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General Information:

Id:	1,957
Diseases:	Alzheimer disease - [OMIM]
Organism:	Mammalia
Publication type:	review
Reference:	Gibson GE et al.(2008) Oxidant-induced changes in mitochondria and calcium dynamics in the pathophysiology of Alzheimers disease Ann. N. Y. Acad. Sci. 1147: 221-232 [PMID: 19076444]

Interaction Information:

Comment	AD does not occur without a reduction in metabolism.
Formal Description Interaction-ID: 15154	phenotype decreased metabolic process increases_activity of disease Alzheimer disease in brain

Comment	Reductions in metabolism correlate with apolipoprotein E (APOE) epsilon4 gene dose and are progressive in late-middle-aged persons.
Formal Description Interaction-ID: 15166	gene/protein mutant APOE (isoform E4) decreases_activity of process metabolic process progressive in late-middle-aged persons

Comment	Reductions in metabolism correlate with apolipoprotein E (APOE)epsilon4 gene dose and are progressive in late-middle-aged persons.
Formal Description Interaction-ID: 15180	process aging decreases_activity of process metabolic process

Comment	Oxidative stress is closely coupled to metabolism since disruptions in metabolism lead to increased free radical production and probably impair free radical removal (quenching).
Formal Description Interaction-ID: 15181	phenotype decreased metabolic process increases_activity of process response to oxidative stress disruptions in metabolism lead to increased free radical production

Comment	Sources of oxidative stress in the brain: Free radicals or reactive oxygen species (ROS) include superoxide, hydroxyl radical, nitric oxide, peroxynitrite, and hydroperoxyl radicals.
Formal Description Interaction-ID: 15183	drug/chemical compound Reactive oxygen species increases_activity of process response to oxidative stress

Comment	Sources of oxidative stress in the brain are free radicals or reactive oxygen species (ROS) include superoxide, hydroxyl radical, nitric oxide, peroxynitrite, and hydroperoxyl radicals.
Formal Description Interaction-ID: 15184	drug/chemical compound Free radical increases_activity of process response to oxidative stress

Comment	Sources of oxidative stress in the brain are free radicals or reactive oxygen species (ROS) include superoxide, hydroxyl radical, nitric oxide, peroxynitrite, and hydroperoxyl radicals.
Formal Description Interaction-ID: 15185	drug/chemical compound O2- increases_activity of process response to oxidative stress

Comment	Sources of oxidative stress in the brain are free radicals or reactive oxygen species (ROS) include superoxide, hydroxyl radical, nitric oxide, peroxynitrite, and hydroperoxyl radicals.
Formal Description Interaction-ID: 15189	drug/chemical compound NO increases_activity of process response to oxidative stress

Comment	Sources of oxidative stress in the brain are free radicals or reactive oxygen species (ROS) include superoxide, hydroxyl radical, nitric oxide, peroxynitrite, and hydroperoxyl radicals.
Formal Description Interaction-ID: 15194	drug/chemical compound Peroxynitrite increases_activity of process response to oxidative stress

Comment	Mitochondrial ROS can originate from multiple reactions in the tricarboxylic acid (TCA) cycle and/or the respiratory chain.
Formal Description Interaction-ID: 15197	process tricarboxylic acid cycle increases_quantity of drug/chemical compound Reactive oxygen species in mitochondria; originating from multiple reactions in the tricarboxylic acid (TCA) cycle and/or the respiratory chain

Comment	Mitochondrial ROS can originate from multiple reactions in the tricarboxylic acid (TCA) cycle and/or the respiratory chain.
Formal Description Interaction-ID: 15202	process respiratory electron transport chain increases_quantity of drug/chemical compound Reactive oxygen species in mitochondria; originating from multiple reactions in the tricarboxylic acid (TCA) cycle and/or the respiratory chain

Comment	Perturbations in metabolism generally exaggerate ROS production.
Formal Description Interaction-ID: 15236	phenotype altered metabolic process increases_quantity of drug/chemical compound Reactive oxygen species

Comment	Antibodies to acrolein (a very reactive aldehyde product of lipid peroxidation) reveals oxidatively modified proteins around the areas of plaques and tangles and also in other areas.
Formal Description Interaction-ID: 15237	drug/chemical compound Acrolein interacts (colocalizes) with phenotype amyloid beta deposits in AD patients

Comment	Antibodies to acrolein (a very reactive aldehyde product of lipid peroxidation) reveals oxidatively modified proteins around the areas of plaques and tangles and also in other areas.
Formal Description Interaction-ID: 15238	drug/chemical compound Acrolein interacts (colocalizes) with phenotype neurofibrillary tangles in AD patients

Comment	Lipoxygenase, a marker of oxidative stress, is increased in brains of AD patients.
Formal Description Interaction-ID: 15239	process response to oxidative stress increases_activity of gene/protein Lipoxygenase in brain of AD patients

Comment	Lipoxygenase, a marker of oxidative stress, is increased in brains of AD patients.
Formal Description Interaction-ID: 15240	gene/protein Lipoxygenase is localized in tissue/cell line brain of AD patients

Comment	Inhibition of energy metabolism by various pharmacological agents, such as insulin, 2-deoxyglucose, 3-nitropropionic acid (3-NP), or kainic acid, elevates beta-secretase levels and enhances plaque pathology in Tg2576 transgenic mice.
Formal Description Interaction-ID: 15241	drug/chemical compound 2-Deoxy-D-glucose decreases_activity of process energy homeostasis in Tg2576 transgenic mice; elevating beta-secretase levels and enhancing plaque pathology

Comment	Inhibition of energy metabolism by various pharmacological agents, such as insulin, 2-deoxyglucose, 3-nitropropionic acid (3-NP), or kainic acid, elevates beta-secretase levels and enhances plaque pathology in Tg2576 transgenic mice.
Formal Description Interaction-ID: 15244	complex/PPI Insulin decreases_activity of process energy homeostasis in Tg2576 transgenic mice; via inhibition of energy metabolism, elevating beta-secretase levels and enhancing plaque pathology

Comment	Inhibition of energy metabolism by various pharmacological agents, such as insulin, 2-deoxyglucose, 3-nitropropionic acid (3-NP), or kainic acid, elevates beta-secretase levels and enhances plaque pathology in Tg2576 transgenic mice.
Formal Description Interaction-ID: 15245	drug/chemical compound beta-Nitropropanoate decreases_activity of process energy homeostasis in Tg2576 transgenic mice; via inhibition of energy metabolism, elevating beta-secretase levels and enhancing plaque pathology

Comment	Inhibition of energy metabolism by various pharmacological agents, such as insulin, 2-deoxyglucose, 3-nitropropionic acid (3-NP), or kainic acid, elevates beta-secretase levels and enhances plaque pathology in Tg2576 transgenic mice.
Formal Description Interaction-ID: 15246	drug/chemical compound Kainic acid decreases_activity of process energy homeostasis in Tg2576 transgenic mice; via inhibition of energy metabolism, elevating beta-secretase levels and enhancing plaque pathology

Comment	Inhibition of energy metabolism by various pharmacological agents, such as insulin, 2-deoxyglucose, 3-nitropropionic acid (3-NP),or kainic acid, elevates beta-secretase levels and enhances plaque pathology in Tg2576 transgenic mice.
Formal Description Interaction-ID: 15248	drug/chemical compound 2-Deoxy-D-glucose increases_quantity of gene/protein BACE1 in Tg2576 transgenic mice
Drugbank entries	Show/Hide entries for BACE1
Drugbank DB02378	MMI-175 not specified BACE1
Drugbank DB06930	N-[amino(imino)methyl]-2-(2,5-diphenyl-1 ... not specified BACE1
Drugbank DB07019	N-[(5R,14R)-5-AMINO-5,14-DIMETHYL-4-OXO- ... not specified BACE1
Drugbank DB07089	N-[amino(imino)methyl]-2-[2-(2-chlorophe ... not specified BACE1
Drugbank DB07110	4-(4-FLUOROBENZYL)PIPERIDINE not specified BACE1
Drugbank DB07175	N-{2-methyl-5-[(6-phenylpyrimidin-4-yl)a ... not specified BACE1
Drugbank DB07206	6-[2-(1H-INDOL-6-YL)ETHYL]PYRIDIN-2-AMIN ... not specified BACE1
Drugbank DB07245	6-[2-(3'-METHOXYBIPHENYL-3-YL)ETHYL]PYRI ... not specified BACE1
Drugbank DB07281	N~3~-BENZYLPYRIDINE-2,3-DIAMINE not specified BACE1
Drugbank DB07284	N~3~-(3-PYRIDIN-3-YLBENZYL)PYRIDINE-2,3- ... not specified BACE1
Drugbank DB07303	N~3~-[3-(5-METHOXYPYRIDIN-3-YL)BENZYL]PY ... not specified BACE1
Drugbank DB07345	4-(2-aminoethyl)-2-cyclohexylphenol not specified BACE1
Drugbank DB07346	4-(2-aminoethyl)-2-ethylphenol not specified BACE1
Drugbank DB07415	4-[(1S)-1-(3-fluoro-4-methoxyphenyl)-2-( ... not specified BACE1
Drugbank DB07519	(6R)-2-amino-6-[2-(3'-methoxybiphenyl-3- ... not specified BACE1
Drugbank DB07535	2-amino-6-[2-(1H-indol-6-yl)ethyl]pyrimi ... not specified BACE1
Drugbank DB07573	(2S)-1-(2,5-dimethylphenoxy)-3-morpholin ... not specified BACE1
Drugbank DB07734	N-(1-benzylpiperidin-4-yl)-4-sulfanylbut ... not specified BACE1
Drugbank DB07735	N-[1-(2,6-dimethoxybenzyl)piperidin-4-yl ... not specified BACE1
Drugbank DB07736	(2S)-4-(4-fluorobenzyl)-N-(2-sulfanyleth ... not specified BACE1
Drugbank DB07737	(2S)-4-(4-fluorobenzyl)-N-(3-sulfanylpro ... not specified BACE1
Drugbank DB07738	N-[1-(5-bromo-2,3-dimethoxybenzyl)piperi ... not specified BACE1
Drugbank DB07874	(6S)-2-amino-6-(3'-methoxybiphenyl-3-yl) ... not specified BACE1
Drugbank DB07993	N~3~-[3-(1H-INDOL-6-YL)BENZYL]PYRIDINE-2 ... not specified BACE1
Drugbank DB07994	N~3~-[5-(1H-INDOL-6-YL)-2-(PYRIDIN-2-YLM ... not specified BACE1
Drugbank DB08749	3-(2-AMINO-6-BENZOYLQUINAZOLIN-3(4H)-YL) ... not specified BACE1
Drugbank DB02378	MMI-175 not specified BACE1

Comment	Inhibition of energy metabolism by various pharmacological agents, such as insulin, 2-deoxyglucose, 3-nitropropionic acid (3-NP),or kainic acid, elevates beta-secretase levels and enhances plaque pathology in Tg2576 transgenic mice.
Formal Description Interaction-ID: 15249	complex/PPI Insulin increases_quantity of gene/protein BACE1 in Tg2576 transgenic mice
Drugbank entries	Show/Hide entries for BACE1
Drugbank DB02378	MMI-175 not specified BACE1
Drugbank DB06930	N-[amino(imino)methyl]-2-(2,5-diphenyl-1 ... not specified BACE1
Drugbank DB07019	N-[(5R,14R)-5-AMINO-5,14-DIMETHYL-4-OXO- ... not specified BACE1
Drugbank DB07089	N-[amino(imino)methyl]-2-[2-(2-chlorophe ... not specified BACE1
Drugbank DB07110	4-(4-FLUOROBENZYL)PIPERIDINE not specified BACE1
Drugbank DB07175	N-{2-methyl-5-[(6-phenylpyrimidin-4-yl)a ... not specified BACE1
Drugbank DB07206	6-[2-(1H-INDOL-6-YL)ETHYL]PYRIDIN-2-AMIN ... not specified BACE1
Drugbank DB07245	6-[2-(3'-METHOXYBIPHENYL-3-YL)ETHYL]PYRI ... not specified BACE1
Drugbank DB07281	N~3~-BENZYLPYRIDINE-2,3-DIAMINE not specified BACE1
Drugbank DB07284	N~3~-(3-PYRIDIN-3-YLBENZYL)PYRIDINE-2,3- ... not specified BACE1
Drugbank DB07303	N~3~-[3-(5-METHOXYPYRIDIN-3-YL)BENZYL]PY ... not specified BACE1
Drugbank DB07345	4-(2-aminoethyl)-2-cyclohexylphenol not specified BACE1
Drugbank DB07346	4-(2-aminoethyl)-2-ethylphenol not specified BACE1
Drugbank DB07415	4-[(1S)-1-(3-fluoro-4-methoxyphenyl)-2-( ... not specified BACE1
Drugbank DB07519	(6R)-2-amino-6-[2-(3'-methoxybiphenyl-3- ... not specified BACE1
Drugbank DB07535	2-amino-6-[2-(1H-indol-6-yl)ethyl]pyrimi ... not specified BACE1
Drugbank DB07573	(2S)-1-(2,5-dimethylphenoxy)-3-morpholin ... not specified BACE1
Drugbank DB07734	N-(1-benzylpiperidin-4-yl)-4-sulfanylbut ... not specified BACE1
Drugbank DB07735	N-[1-(2,6-dimethoxybenzyl)piperidin-4-yl ... not specified BACE1
Drugbank DB07736	(2S)-4-(4-fluorobenzyl)-N-(2-sulfanyleth ... not specified BACE1
Drugbank DB07737	(2S)-4-(4-fluorobenzyl)-N-(3-sulfanylpro ... not specified BACE1
Drugbank DB07738	N-[1-(5-bromo-2,3-dimethoxybenzyl)piperi ... not specified BACE1
Drugbank DB07874	(6S)-2-amino-6-(3'-methoxybiphenyl-3-yl) ... not specified BACE1
Drugbank DB07993	N~3~-[3-(1H-INDOL-6-YL)BENZYL]PYRIDINE-2 ... not specified BACE1
Drugbank DB07994	N~3~-[5-(1H-INDOL-6-YL)-2-(PYRIDIN-2-YLM ... not specified BACE1
Drugbank DB08749	3-(2-AMINO-6-BENZOYLQUINAZOLIN-3(4H)-YL) ... not specified BACE1
Drugbank DB02378	MMI-175 not specified BACE1

Comment	Inhibition of energy metabolism by various pharmacological agents, such as insulin, 2-deoxyglucose, 3-nitropropionic acid (3-NP), or kainic acid, elevates beta-secretase levels and enhances plaque pathology in Tg2576 transgenic mice.
Formal Description Interaction-ID: 15250	drug/chemical compound beta-Nitropropanoate increases_quantity of gene/protein BACE1 in Tg2576 transgenic mice
Drugbank entries	Show/Hide entries for BACE1
Drugbank DB02378	MMI-175 not specified BACE1
Drugbank DB06930	N-[amino(imino)methyl]-2-(2,5-diphenyl-1 ... not specified BACE1
Drugbank DB07019	N-[(5R,14R)-5-AMINO-5,14-DIMETHYL-4-OXO- ... not specified BACE1
Drugbank DB07089	N-[amino(imino)methyl]-2-[2-(2-chlorophe ... not specified BACE1
Drugbank DB07110	4-(4-FLUOROBENZYL)PIPERIDINE not specified BACE1
Drugbank DB07175	N-{2-methyl-5-[(6-phenylpyrimidin-4-yl)a ... not specified BACE1
Drugbank DB07206	6-[2-(1H-INDOL-6-YL)ETHYL]PYRIDIN-2-AMIN ... not specified BACE1
Drugbank DB07245	6-[2-(3'-METHOXYBIPHENYL-3-YL)ETHYL]PYRI ... not specified BACE1
Drugbank DB07281	N~3~-BENZYLPYRIDINE-2,3-DIAMINE not specified BACE1
Drugbank DB07284	N~3~-(3-PYRIDIN-3-YLBENZYL)PYRIDINE-2,3- ... not specified BACE1
Drugbank DB07303	N~3~-[3-(5-METHOXYPYRIDIN-3-YL)BENZYL]PY ... not specified BACE1
Drugbank DB07345	4-(2-aminoethyl)-2-cyclohexylphenol not specified BACE1
Drugbank DB07346	4-(2-aminoethyl)-2-ethylphenol not specified BACE1
Drugbank DB07415	4-[(1S)-1-(3-fluoro-4-methoxyphenyl)-2-( ... not specified BACE1
Drugbank DB07519	(6R)-2-amino-6-[2-(3'-methoxybiphenyl-3- ... not specified BACE1
Drugbank DB07535	2-amino-6-[2-(1H-indol-6-yl)ethyl]pyrimi ... not specified BACE1
Drugbank DB07573	(2S)-1-(2,5-dimethylphenoxy)-3-morpholin ... not specified BACE1
Drugbank DB07734	N-(1-benzylpiperidin-4-yl)-4-sulfanylbut ... not specified BACE1
Drugbank DB07735	N-[1-(2,6-dimethoxybenzyl)piperidin-4-yl ... not specified BACE1
Drugbank DB07736	(2S)-4-(4-fluorobenzyl)-N-(2-sulfanyleth ... not specified BACE1
Drugbank DB07737	(2S)-4-(4-fluorobenzyl)-N-(3-sulfanylpro ... not specified BACE1
Drugbank DB07738	N-[1-(5-bromo-2,3-dimethoxybenzyl)piperi ... not specified BACE1
Drugbank DB07874	(6S)-2-amino-6-(3'-methoxybiphenyl-3-yl) ... not specified BACE1
Drugbank DB07993	N~3~-[3-(1H-INDOL-6-YL)BENZYL]PYRIDINE-2 ... not specified BACE1
Drugbank DB07994	N~3~-[5-(1H-INDOL-6-YL)-2-(PYRIDIN-2-YLM ... not specified BACE1
Drugbank DB08749	3-(2-AMINO-6-BENZOYLQUINAZOLIN-3(4H)-YL) ... not specified BACE1
Drugbank DB02378	MMI-175 not specified BACE1

Comment	Inhibition of energy metabolism by various pharmacological agents, such as insulin, 2-deoxyglucose, 3-nitropropionic acid (3-NP),or kainic acid, elevates beta-secretase levels and enhances plaque pathology in Tg2576 transgenic mice.
Formal Description Interaction-ID: 15251	drug/chemical compound Kainic acid increases_quantity of gene/protein BACE1 in Tg2576 transgenic mice
Drugbank entries	Show/Hide entries for BACE1
Drugbank DB02378	MMI-175 not specified BACE1
Drugbank DB06930	N-[amino(imino)methyl]-2-(2,5-diphenyl-1 ... not specified BACE1
Drugbank DB07019	N-[(5R,14R)-5-AMINO-5,14-DIMETHYL-4-OXO- ... not specified BACE1
Drugbank DB07089	N-[amino(imino)methyl]-2-[2-(2-chlorophe ... not specified BACE1
Drugbank DB07110	4-(4-FLUOROBENZYL)PIPERIDINE not specified BACE1
Drugbank DB07175	N-{2-methyl-5-[(6-phenylpyrimidin-4-yl)a ... not specified BACE1
Drugbank DB07206	6-[2-(1H-INDOL-6-YL)ETHYL]PYRIDIN-2-AMIN ... not specified BACE1
Drugbank DB07245	6-[2-(3'-METHOXYBIPHENYL-3-YL)ETHYL]PYRI ... not specified BACE1
Drugbank DB07281	N~3~-BENZYLPYRIDINE-2,3-DIAMINE not specified BACE1
Drugbank DB07284	N~3~-(3-PYRIDIN-3-YLBENZYL)PYRIDINE-2,3- ... not specified BACE1
Drugbank DB07303	N~3~-[3-(5-METHOXYPYRIDIN-3-YL)BENZYL]PY ... not specified BACE1
Drugbank DB07345	4-(2-aminoethyl)-2-cyclohexylphenol not specified BACE1
Drugbank DB07346	4-(2-aminoethyl)-2-ethylphenol not specified BACE1
Drugbank DB07415	4-[(1S)-1-(3-fluoro-4-methoxyphenyl)-2-( ... not specified BACE1
Drugbank DB07519	(6R)-2-amino-6-[2-(3'-methoxybiphenyl-3- ... not specified BACE1
Drugbank DB07535	2-amino-6-[2-(1H-indol-6-yl)ethyl]pyrimi ... not specified BACE1
Drugbank DB07573	(2S)-1-(2,5-dimethylphenoxy)-3-morpholin ... not specified BACE1
Drugbank DB07734	N-(1-benzylpiperidin-4-yl)-4-sulfanylbut ... not specified BACE1
Drugbank DB07735	N-[1-(2,6-dimethoxybenzyl)piperidin-4-yl ... not specified BACE1
Drugbank DB07736	(2S)-4-(4-fluorobenzyl)-N-(2-sulfanyleth ... not specified BACE1
Drugbank DB07737	(2S)-4-(4-fluorobenzyl)-N-(3-sulfanylpro ... not specified BACE1
Drugbank DB07738	N-[1-(5-bromo-2,3-dimethoxybenzyl)piperi ... not specified BACE1
Drugbank DB07874	(6S)-2-amino-6-(3'-methoxybiphenyl-3-yl) ... not specified BACE1
Drugbank DB07993	N~3~-[3-(1H-INDOL-6-YL)BENZYL]PYRIDINE-2 ... not specified BACE1
Drugbank DB07994	N~3~-[5-(1H-INDOL-6-YL)-2-(PYRIDIN-2-YLM ... not specified BACE1
Drugbank DB08749	3-(2-AMINO-6-BENZOYLQUINAZOLIN-3(4H)-YL) ... not specified BACE1
Drugbank DB02378	MMI-175 not specified BACE1

Comment	Inhibition of energy metabolism by various pharmacological agents, such as insulin, 2-deoxyglucose, 3-nitropropionic acid (3-NP), or kainic acid, elevates beta-secretase levels and enhances plaque pathology in Tg2576 transgenic mice.
Formal Description Interaction-ID: 15253	drug/chemical compound 2-Deoxy-D-glucose increases_quantity of phenotype amyloid beta deposits in Tg2576 transgenic mice

Comment	Inhibition of energy metabolism by various pharmacological agents, such as insulin, 2-deoxyglucose, 3-nitropropionic acid (3-NP), or kainic acid, elevates beta-secretase levels and enhances plaque pathology in Tg2576 transgenic mice.
Formal Description Interaction-ID: 15255	complex/PPI Insulin increases_quantity of phenotype amyloid beta deposits in Tg2576 transgenic mice

Comment	Inhibition of energy metabolism by various pharmacological agents, such as insulin, 2-deoxyglucose, 3-nitropropionic acid (3-NP), or kainic acid, elevates beta-secretase levels and enhances plaque pathology in Tg2576 transgenic mice.
Formal Description Interaction-ID: 15257	drug/chemical compound beta-Nitropropanoate increases_quantity of phenotype amyloid beta deposits in Tg2576 transgenic mice

Comment	Inhibition of energy metabolism by various pharmacological agents, such as insulin, 2-deoxyglucose, 3-nitropropionic acid (3-NP), or kainic acid, elevates beta-secretase levels and enhances plaque pathology in Tg2576 transgenic mice.
Formal Description Interaction-ID: 15258	drug/chemical compound Kainic acid increases_quantity of phenotype amyloid beta deposits in Tg2576 transgenic mice

Comment	Antibodies to acrolein (a very reactive aldehyde product of lipid peroxidation) reveals oxidatively modified proteins around the areas of plaques and tangles and also in other areas.
Formal Description Interaction-ID: 15261	process response to oxidative stress increases_activity of process protein oxidation in AD patients; around the areas of plaques and tangles and also in other areas

Comment	Antibodies to acrolein (a very reactive aldehyde product of lipid peroxidation) reveals oxidatively modified proteins around the areas of plaques and tangles and also in other areas.
Formal Description Interaction-ID: 15263	process lipid peroxidation increases_quantity of drug/chemical compound Acrolein in AD patients; lipid peroxidation affected the quantity of Acrolein

Comment	The activities of the enzymes of the TCA cycle change in brains from patients that died with autopsy-confirmed AD.
Formal Description Interaction-ID: 15271	disease Alzheimer disease affects_activity of process tricarboxylic acid cycle in brain of AD patients; via changing the activities of enzymes of the TCA cycle

Comment	The activities of the pyruvate dehydrogenase complex (PDHC), isocitrate dehydrogenase complex (ICDHC), and the alpha-ketoglutarate dehydrogenase complex (KGDHC) decline significantly in the brains of AD patients.
Formal Description Interaction-ID: 15273	disease Alzheimer disease decreases_activity of complex/PPI Pyruvate dehydrogenase complex in brain of AD patients

Comment	The activities of the pyruvate dehydrogenase complex (PDHC), isocitrate dehydrogenase complex (ICDHC), and the alpha-ketoglutarate dehydrogenase complex (KGDHC) decline significantly in the brains of AD patients.
Formal Description Interaction-ID: 15274	disease Alzheimer disease decreases_activity of complex/PPI Isocitrate dehydrogenase in brain of AD patients

Comment	The activities of the pyruvate dehydrogenase complex (PDHC), isocitrate dehydrogenase complex (ICDHC), and the alpha-ketoglutarate dehydrogenase complex (KGDHC) decline significantly in the brains of AD patients.
Formal Description Interaction-ID: 15275	disease Alzheimer disease decreases_activity of complex/PPI Oxoglutarate dehydrogenase in brain of AD patients

Comment	In the brains of AD patients activities of succinate dehydrogenase (SDH) (complex II) and malate dehydrogenase (MDH) are elevated.
Formal Description Interaction-ID: 15276	disease Alzheimer disease increases_activity of gene/protein SDHA
Drugbank entries	Show/Hide entries for SDHA
Drugbank DB00139	Succinic acid not specified SDHA
Drugbank DB04141	2-Hexyloxy-6-Hydroxymethyl-Tetrahydro-Py ... not specified SDHA
Drugbank DB04631	Atpenin A5 not specified sdhA
Drugbank DB04657	Carboxin not specified SDHA
Drugbank DB04795	Thenoyltrifluoroacetone not specified SDHA
Drugbank DB07671	2-[1-METHYLHEXYL]-4,6-DINITROPHENOL not specified sdhA
Drugbank DB08689	UBIQUINONE-1 not specified SDHA
Drugbank DB08690	UBIQUINONE-2 not specified sdhA
Drugbank DB00139	Succinic acid not specified SDHA
Drugbank DB04631	Atpenin A5 not specified sdhA
Drugbank DB04657	Carboxin not specified SDHA
Drugbank DB04795	Thenoyltrifluoroacetone not specified SDHA

Comment	In the brains of AD patients activities of succinate dehydrogenase (SDH) (complex II) and malate dehydrogenase (MDH) are elevated.
Formal Description Interaction-ID: 15277	disease Alzheimer disease increases_activity of gene/protein MDH2
Drugbank entries	Show/Hide entries for MDH2
Drugbank DB00157	NADH not specified MDH2
Drugbank DB04272	Citric Acid not specified MDH2
Drugbank DB00157	NADH not specified MDH2
Drugbank DB04272	Citric Acid not specified MDH2

Comment	In brains from patients that died bearing the APP670/671 mutation, the protein levels of E1k and E2k are diminished.
Formal Description Interaction-ID: 15294	gene/protein mutant APP-p.KM670/671NL decreases_quantity of gene/protein OGDH in brain
Drugbank entries	Show/Hide entries for OGDH
Drugbank DB00157	NADH not specified OGDH
Drugbank DB00157	NADH not specified OGDH

Comment	In brains from patients that died bearing the APP670/671 mutation, the protein levels of E1k and E2k are diminished.
Formal Description Interaction-ID: 15296	gene/protein mutant APP-p.KM670/671NL decreases_quantity of gene/protein DLST in brain

Comment	KGDHC (alpha-ketoglutaric acid dehydrogenase complex) is inactivated by a variety of oxidants, including peroxynitrite, NO, hydroxynonenal, H2O2, chloroamine, and sodium hypochlorite.
Formal Description Interaction-ID: 15298	drug/chemical compound Peroxynitrite decreases_activity of complex/PPI Oxoglutarate dehydrogenase

Comment	KGDHC (alpha-ketoglutaric acid dehydrogenase complex) is inactivated by a variety of oxidants, including peroxynitrite, NO, hydroxynonenal, H2O2, chloroamine, and sodium hypochlorite.
Formal Description Interaction-ID: 15299	drug/chemical compound NO decreases_activity of complex/PPI Oxoglutarate dehydrogenase

Comment	KGDHC (alpha-ketoglutaric acid dehydrogenase complex) is inactivated by a variety of oxidants, including peroxynitrite, NO, hydroxynonenal, H2O2, chloroamine, and sodium hypochlorite. KGDHC in intact mitochondria is inactivated by hydroxynonenal (HNE), a marker of oxidative stress that is elevated in brains of both AD patients and animals with impaired brain metabolism because of thiamine deficiency.
Formal Description Interaction-ID: 15301	drug/chemical compound Hydroxynonenal decreases_activity of complex/PPI Oxoglutarate dehydrogenase

Comment	KGDHC (alpha-ketoglutaric acid dehydrogenase complex) is inactivated by a variety of oxidants, including peroxynitrite, NO, hydroxynonenal, H2O2, chloroamine, and sodium hypochlorite. H2O2 diminishes KGDHC activity in synaptosomes, fibroblasts, and N2a cells.
Formal Description Interaction-ID: 15303	drug/chemical compound H2O2 decreases_activity of complex/PPI Oxoglutarate dehydrogenase in synaptosomes, fibroblasts, and N2a cells

Comment	KGDHC (alpha-ketoglutaric acid dehydrogenase complex) is inactivated by a variety of oxidants, including peroxynitrite, NO, hydroxynonenal, H2O2, chloroamine, and sodium hypochlorite.
Formal Description Interaction-ID: 15304	drug/chemical compound Chloroamine decreases_activity of complex/PPI Oxoglutarate dehydrogenase

Comment	KGDHC (alpha-ketoglutaric acid dehydrogenase complex) is inactivated by a variety of oxidants, including peroxynitrite, NO, hydroxynonenal, H2O2, chloroamine, and sodium hypochlorite.
Formal Description Interaction-ID: 15305	drug/chemical compound Sodium hypochlorite decreases_activity of complex/PPI Oxoglutarate dehydrogenase

Comment	Hydroxynonenal (HNE) is a marker of oxidative stress that is elevated in brains of both AD patients and animals with impaired brain metabolism because of thiamine deficiency.
Formal Description Interaction-ID: 15306	process response to oxidative stress increases_quantity of drug/chemical compound Hydroxynonenal elevated in brains of both AD patients and animals with impaired brain metabolism

Comment	Hydroxynonenal (HNE) is a marker of oxidative stress that is elevated in brains of both AD patients and animals with impaired brain metabolism because of thiamine deficiency.
Formal Description Interaction-ID: 15307	drug/chemical compound Hydroxynonenal is localized in tissue/cell line brain in AD patients

Comment	Hydroxynonenal (HNE) is a marker of oxidative stress that is elevated in brains of both AD patients and animals with impaired brain metabolism because of thiamine deficiency.
Formal Description Interaction-ID: 15308	disease Alzheimer disease increases_quantity of drug/chemical compound Hydroxynonenal marker of oxidative stress

Comment	In brains from patients that died bearing the APP670/671 mutation, the protein levels of E1k and E2k are diminished.
Formal Description Interaction-ID: 15309	gene/protein mutant APP-p.KM670/671NL affects_activity of gene/protein APP
Drugbank entries	Show/Hide entries for APP
Drugbank DB02235	Methionine Sulfoxide not specified APP
Drugbank DB02235	Methionine Sulfoxide not specified APP

Comment	PDHC, ICDHC, and KGDHC - these enzymes are the entry steps of substrates into the TCA cycle and form the first half of the TCA cycle.
Formal Description Interaction-ID: 15310	complex/PPI Pyruvate dehydrogenase complex increases_activity of process tricarboxylic acid cycle

Comment	PDHC, ICDHC, and KGDHC - these enzymes are the entry steps of substrates into the TCA cycle and form the first half of theTCA cycle.
Formal Description Interaction-ID: 15311	complex/PPI Oxoglutarate dehydrogenase increases_activity of process tricarboxylic acid cycle

Comment	In brains from patients that died bearing the APP670/671 mutation, the protein levels of E1k and E2k are diminished. KGDHC is a multi-enzyme complex that consists of an ordered array of multiple copies of three proteins: alpha-ketoglutarate dehydrogenase (E1k, EC 1.2.4.2), dihydrolipoyl succinyltransferase (E2k, EC 2.3.1.61), and dihydrolipoyl dehydrogenase (E3, EC 1.8.1.4).
Formal Description Interaction-ID: 15313	gene/protein OGDH is_part_of complex/PPI Oxoglutarate dehydrogenase in brain
Drugbank entries	Show/Hide entries for OGDH
Drugbank DB00157	NADH not specified OGDH
Drugbank DB00157	NADH not specified OGDH

Comment	In brains from patients that died bearing the APP670/671 mutation, the protein levels of E1k and E2k are diminished. KGDHC is a multi-enzyme complex that consists of an ordered array of multiple copies of three proteins: alpha-ketoglutarate dehydrogenase (E1k, EC 1.2.4.2), dihydrolipoyl succinyltransferase (E2k, EC 2.3.1.61), and dihydrolipoyl dehydrogenase (E3, EC 1.8.1.4).
Formal Description Interaction-ID: 15314	gene/protein DLST is_part_of complex/PPI Oxoglutarate dehydrogenase in brain

Comment	PDHC, ICDHC, and KGDHC - these enzymes are the entry steps of substrates into the TCA cycle and form the first half of theTCA cycle.
Formal Description Interaction-ID: 15315	complex/PPI Isocitrate dehydrogenase increases_activity of process tricarboxylic acid cycle

Comment	KGDHC is a multi-enzyme complex that consists of an ordered array of multiple copies of three proteins: alpha-ketoglutarate dehydrogenase (E1k, EC 1.2.4.2), dihydrolipoyl succinyltransferase (E2k, EC 2.3.1.61), and dihydrolipoyl dehydrogenase (E3, EC 1.8.1.4).
Formal Description Interaction-ID: 15316	gene/protein DLD affects_activity of complex/PPI Oxoglutarate dehydrogenase
Drugbank entries	Show/Hide entries for DLD
Drugbank DB00157	NADH not specified DLD
Drugbank DB00756	Hexachlorophene inhibitor dld
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified DLD
Drugbank DB03147	Flavin-Adenine Dinucleotide not specified dld
Drugbank DB03147	Flavin-Adenine Dinucleotide not specified DLD
Drugbank DB00157	NADH not specified DLD
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified DLD
Drugbank DB03147	Flavin-Adenine Dinucleotide not specified dld
Drugbank DB03147	Flavin-Adenine Dinucleotide not specified DLD

Comment	Treatment of KGDHC with increasing concentrations of GSSG progressively enhances glutathionylation of E1k, E2k, and E3.
Formal Description Interaction-ID: 15317	drug/chemical compound Glutathione disulfide affects_activity of complex/PPI Oxoglutarate dehydrogenase with increasing concentrations of GSSG

Comment	KGDHC is regulated by glutathione.
Formal Description Interaction-ID: 15318	drug/chemical compound Glutathione affects_activity of complex/PPI Oxoglutarate dehydrogenase
Drugbank entries	Show/Hide entries for Glutathione
Drugbank DB00143	Glutathione not specified GSR
Drugbank DB00143	Glutathione not specified GSS
Drugbank DB00143	Glutathione not specified GSTM1
Drugbank DB00143	Glutathione not specified GSTK1
Drugbank DB00143	Glutathione not specified GSTA3
Drugbank DB00143	Glutathione not specified GSTM3
Drugbank DB00143	Glutathione not specified GSTA4
Drugbank DB00143	Glutathione not specified GSTM4
Drugbank DB00143	Glutathione not specified GSTA5
Drugbank DB00143	Glutathione not specified GSTP1
Drugbank DB00143	Glutathione not specified GSTO1
Drugbank DB00143	Glutathione cofactor GPX1
Drugbank DB00143	Glutathione cofactor GPX2
Drugbank DB00143	Glutathione not specified GSTT1
Drugbank DB00143	Glutathione not specified GSTZ1
Drugbank DB00143	Glutathione cofactor GPX5
Drugbank DB00143	Glutathione cofactor GPX3
Drugbank DB00143	Glutathione not specified GLO1
Drugbank DB00143	Glutathione not specified LTC4S
Drugbank DB00143	Glutathione not specified MGST3
Drugbank DB00143	Glutathione not specified HPGDS
Drugbank DB00143	Glutathione not specified TXNDC12
Drugbank DB00143	Glutathione not specified GSTA1
Drugbank DB00143	Glutathione not specified GSTA2
Drugbank DB00143	Glutathione not specified MGST1
Drugbank DB00143	Glutathione not specified ESD
Drugbank DB00143	Glutathione not specified GGT1
Drugbank DB00143	Glutathione not specified GSTM2
Drugbank DB00143	Glutathione not specified GLRX
Drugbank DB00143	Glutathione cofactor GPX4
Drugbank DB00143	Glutathione not specified GSTM5
Drugbank DB00143	Glutathione cofactor GPX6
Drugbank DB00143	Glutathione not specified HAGH
Drugbank DB00143	Glutathione not specified GPX1
Drugbank DB00143	Glutathione cofactor GPX4
Drugbank DB00143	Glutathione not specified GPX8
Drugbank DB00143	Glutathione cofactor GPX7
Drugbank DB00143	Glutathione not specified MGST2
Drugbank DB00143	Glutathione not specified GSTO2
Drugbank DB00143	Glutathione not specified GLRX2
Drugbank DB00143	Glutathione not specified MGST3
Drugbank DB00143	Glutathione not specified HPGDS
Drugbank DB00143	Glutathione not specified TXNDC12
Drugbank DB00143	Glutathione not specified GSTA1
Drugbank DB00143	Glutathione not specified GSTA2
Drugbank DB00143	Glutathione not specified MGST1
Drugbank DB00143	Glutathione not specified ESD
Drugbank DB00143	Glutathione not specified GGT1
Drugbank DB00143	Glutathione not specified GSTM2
Drugbank DB00143	Glutathione not specified GLRX
Drugbank DB00143	Glutathione cofactor GPX4
Drugbank DB00143	Glutathione not specified GSTM5
Drugbank DB00143	Glutathione cofactor GPX6
Drugbank DB00143	Glutathione not specified HAGH
Drugbank DB00143	Glutathione not specified GPX1
Drugbank DB00143	Glutathione cofactor GPX4
Drugbank DB00143	Glutathione not specified GPX8
Drugbank DB00143	Glutathione cofactor GPX7
Drugbank DB00143	Glutathione not specified MGST2
Drugbank DB00143	Glutathione not specified GSTO2
Drugbank DB00143	Glutathione not specified GLRX2
Drugbank DB00143	Glutathione not specified GLO1
Drugbank DB00143	Glutathione not specified LTC4S
Drugbank DB00143	Glutathione not specified GSR
Drugbank DB00143	Glutathione not specified GSS
Drugbank DB00143	Glutathione not specified GSTM1
Drugbank DB00143	Glutathione not specified GSTK1
Drugbank DB00143	Glutathione not specified GSTA3
Drugbank DB00143	Glutathione not specified GSTM3
Drugbank DB00143	Glutathione not specified GSTA4
Drugbank DB00143	Glutathione not specified GSTM4
Drugbank DB00143	Glutathione not specified GSTA5
Drugbank DB00143	Glutathione not specified GSTP1
Drugbank DB00143	Glutathione not specified GSTO1
Drugbank DB00143	Glutathione cofactor GPX1
Drugbank DB00143	Glutathione cofactor GPX2
Drugbank DB00143	Glutathione not specified GSTT1
Drugbank DB00143	Glutathione not specified GSTZ1
Drugbank DB00143	Glutathione cofactor GPX5
Drugbank DB00143	Glutathione cofactor GPX3

Comment	Treatment of KGDHC with increasing concentrations of GSSG progressively enhances glutathionylation of E1k, E2k, and E3.
Formal Description Interaction-ID: 15319	drug/chemical compound Glutathione disulfide increases_modification of gene/protein OGDH via glutathionylation of E1K
Drugbank entries	Show/Hide entries for OGDH
Drugbank DB00157	NADH not specified OGDH
Drugbank DB00157	NADH not specified OGDH

Comment	Treatment of KGDHC with increasing concentrations of GSSG progressively enhances glutathionylation of E1k, E2k, and E3.
Formal Description Interaction-ID: 15320	drug/chemical compound Glutathione disulfide increases_modification of gene/protein DLST via glutathionylation of E2K

Comment	Treatment of KGDHC with increasing concentrations of GSSG progressively enhances glutathionylation of E1k, E2k, and E3.
Formal Description Interaction-ID: 15322	drug/chemical compound Glutathione disulfide increases_modification of gene/protein DLD via glutathionylation of E3
Drugbank entries	Show/Hide entries for DLD
Drugbank DB00157	NADH not specified DLD
Drugbank DB00756	Hexachlorophene inhibitor dld
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified DLD
Drugbank DB03147	Flavin-Adenine Dinucleotide not specified dld
Drugbank DB03147	Flavin-Adenine Dinucleotide not specified DLD
Drugbank DB00157	NADH not specified DLD
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified DLD
Drugbank DB03147	Flavin-Adenine Dinucleotide not specified dld
Drugbank DB03147	Flavin-Adenine Dinucleotide not specified DLD

Comment	The H2O2-induced increase in ROS and cell death is greater in cells with diminished E2k than in controls.
Formal Description Interaction-ID: 15323	phenotype decreased DLST level increases_quantity of drug/chemical compound Reactive oxygen species concerning H2O2-induced increase in ROS and cell death

Comment	The H2O2-induced increase in ROS and cell death is greater in cells with diminished E2k than in controls.
Formal Description Interaction-ID: 15325	drug/chemical compound H2O2 increases_quantity of drug/chemical compound Reactive oxygen species

Comment	The H2O2-induced increase in ROS and cell death is greater in cells with diminished E2k than in controls.
Formal Description Interaction-ID: 15326	drug/chemical compound H2O2 increases_activity of process neuron death

Comment	The H2O2-induced increase in ROS and cell death is greater in cells with diminished E2k than in controls.
Formal Description Interaction-ID: 15327	drug/chemical compound Reactive oxygen species increases_activity of process neuron death

Comment	Under reducing conditions KGDHC is the primary source of H2O2 in mitochondria.
Formal Description Interaction-ID: 15494	complex/PPI Oxoglutarate dehydrogenase increases_quantity of drug/chemical compound H2O2 in mitochondria; under reducing conditions

Comment	MDH activity varies with the E2k levels in cells with variable Ek2 protein levels.
Formal Description Interaction-ID: 15495	gene/protein DLST affects_activity of gene/protein MDH depending on E2K level
Drugbank entries	Show/Hide entries for MDH
Drugbank DB00336	Nitrofurazone inhibitor mdh
Drugbank DB01677	Fumarate not specified mdh
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified mdh
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified mdh
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified mdh
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified mdh
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified mdh
Drugbank DB02637	Oxaloacetate Ion not specified mdh
Drugbank DB00336	Nitrofurazone inhibitor mdh
Drugbank DB01677	Fumarate not specified mdh
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified mdh
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified mdh
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified mdh
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified mdh
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified mdh
Drugbank DB02637	Oxaloacetate Ion not specified mdh

Comment	Cellular calcium dynamics are altered in cells from patients with AD.
Formal Description Interaction-ID: 15496	disease Alzheimer disease affects_activity of process calcium ion transport

Comment	Fibroblasts from AD patients or from presenilin-1 transgenic mice have exaggerated ER calcium stores.
Formal Description Interaction-ID: 15497	disease Alzheimer disease increases_activity of process positive regulation of endoplasmic reticulum calcium ion concentration in fibroblasts from AD patients or from presenilin-1 transgenic mice

Comment	Fibroblasts from AD patients or from presenilin-1 transgenic mice have diminished mitochondrial calcium uptake.
Formal Description Interaction-ID: 15498	disease Alzheimer disease increases_activity of process negative regulation of mitochondrial calcium ion concentration in fibroblasts from AD patients or from presenilin-1 transgenic mice

Comment	A selective inhibitor of KGDHC is alpha-keto-beta-methyl valerate (KMV).
Formal Description Interaction-ID: 15503	drug/chemical compound Alpha-keto-beta-methyl valerate decreases_activity of complex/PPI Oxoglutarate dehydrogenase

Comment	Inhibitors of KGDHC release cytochrome C from the mitochondria to the cytosol, activate caspases and alter ER calcium stores before they cause a decline the mitochondrial membrane potentials (a measure of mitochondrial function).
Formal Description Interaction-ID: 15508	complex/PPI Oxoglutarate dehydrogenase decreases_activity of process release of cytochrome c from mitochondria to the cytosol

Comment	A selective inhibitor of KGDHC is alpha-keto-beta-methyl valerate (KMV). Inhibitors of KGDHC alter ER calcium stores before they cause a decline of the mitochondrial membrane potentials (a measure of mitochondrial function).
Formal Description Interaction-ID: 15510	drug/chemical compound Alpha-keto-beta-methyl valerate affects_activity of process endoplasmic reticulum calcium ion homeostasis

Comment	A selective inhibitor of KGDHC is alpha-keto-beta-methyl valerate (KMV), Inhibitors of KGDHC alter ER calcium stores before they cause a decline of the mitochondrial membrane potentials (a measure of mitochondrial function).
Formal Description Interaction-ID: 15512	drug/chemical compound Alpha-keto-beta-methyl valerate decreases_activity of process mitochondrial depolarization

Comment	Malondialdehyde, a common measure of oxidative stress, is elevated in the brains of Dld+/- mice.
Formal Description Interaction-ID: 15527	disease Alzheimer disease increases_quantity of drug/chemical compound Malonaldehyde in brain of Dld+/- mice
Drugbank entries	Show/Hide entries for
Drugbank DB03057	Malonaldehyde not specified bla
Drugbank DB03057	Malonaldehyde not specified bla

Comment	Malondialdehyde, a common measure of oxidative stress, is elevated in the brains of Dld+/- mice.
Formal Description Interaction-ID: 15528	process response to oxidative stress increases_quantity of drug/chemical compound Malonaldehyde
Drugbank entries	Show/Hide entries for
Drugbank DB03057	Malonaldehyde not specified bla
Drugbank DB03057	Malonaldehyde not specified bla

Comment	A reduction in KGDHC activity can impair memory in the emotional domain.
Formal Description Interaction-ID: 15529	phenotype decreased oxoglutarate dehydrogenase activity decreases_activity of process learning or memory in the emotional domain

Comment	Lipoxygenase, a marker of oxidative stress, is increased in brains of AD patients.
Formal Description Interaction-ID: 127813	disease Alzheimer disease increases_quantity of gene/protein Lipoxygenase in brain of AD patients; a marker of oxidative stress

Comment	In brains from patients that died bearing the APP670/671 mutation, the protein levels of E1k and E2k are diminished. KGDHC is a multi-enzyme complex that consists of an ordered array of multiple copies of three proteins: alpha-ketoglutarate dehydrogenase (E1k, EC 1.2.4.2), dihydrolipoyl succinyltransferase (E2k, EC 2.3.1.61), and dihydrolipoyl dehydrogenase (E3, EC 1.8.1.4).
Formal Description Interaction-ID: 127816	disease Alzheimer disease decreases_quantity of gene/protein OGDH in AD brain
Drugbank entries	Show/Hide entries for OGDH
Drugbank DB00157	NADH not specified OGDH
Drugbank DB00157	NADH not specified OGDH

Comment	In brains from patients that died bearing the APP670/671 mutation, the protein levels of E1k and E2k are diminished. KGDHC is a multi-enzyme complex that consists of an ordered array of multiple copies of three proteins: alpha-ketoglutarate dehydrogenase (E1k, EC 1.2.4.2), dihydrolipoyl succinyltransferase (E2k, EC 2.3.1.61), and dihydrolipoyl dehydrogenase (E3, EC 1.8.1.4).
Formal Description Interaction-ID: 127817	disease Alzheimer disease decreases_quantity of gene/protein DLST in AD brain bearing the APP670/671 mutation