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General Information:

Id:	15,346
Diseases:	Alzheimer disease - [OMIM]
Organism:	Mammalia
Publication type:	review
Reference:	[PMID: 32397599]

Interaction Information:

Comment	Treatment of various autophagy-inducing agents enhances the clearance of aggregate-prone proteins in an mTOR-dependent or -independent manner. The mTOR-dependent autophagy inducers, rapamycin and curcumin, directly inhibit mTORC1 activity, resulting in activation of the ULK1 complex. Conversely, mTOR-independent agents upregulate autophagy activity through various intracellular signaling cascade or lysosome biogenesis.
Formal Description Interaction-ID: 145064	drug/chemical compound Rapamycin increases_activity of process autophagy in an mTOR-dependent manner

Comment	Treatment of various autophagy-inducing agents enhances the clearance of aggregate-prone proteins in an mTOR-dependent or -independent manner. The mTOR-dependent autophagy inducers, rapamycin and curcumin, directly inhibit mTORC1 activity, resulting in activation of the ULK1 complex. Conversely, mTOR-independent agents upregulate autophagy activity through various intracellular signaling cascade or lysosome biogenesis.
Formal Description Interaction-ID: 145066	drug/chemical compound Curcumin increases_activity of process autophagy in an mTOR-dependent manner

Comment	Treatment of various autophagy-inducing agents enhances the clearance of aggregate-prone proteins in an mTOR-dependent or -independent manner. The mTOR-dependent autophagy inducers, rapamycin and curcumin, directly inhibit mTORC1 activity, resulting in activation of the ULK1 complex. Conversely, mTOR-independent agents upregulate autophagy activity through various intracellular signaling cascade or lysosome biogenesis.
Formal Description Interaction-ID: 145067	drug/chemical compound Rapamycin decreases_activity of complex/PPI mTORC1 complex resulting in activation of the ULK1 complex

Comment	Treatment of various autophagy-inducing agents enhances the clearance of aggregate-prone proteins in an mTOR-dependent or -independent manner. The mTOR-dependent autophagy inducers, rapamycin and curcumin, directly inhibit mTORC1 activity, resulting in activation of the ULK1 complex. Conversely, mTOR-independent agents upregulate autophagy activity through various intracellular signaling cascade or lysosome biogenesis.
Formal Description Interaction-ID: 145068	drug/chemical compound Curcumin decreases_activity of complex/PPI mTORC1 complex resulting in activation of the ULK1 complex

Comment	Treatment of various autophagy-inducing agents enhances the clearance of aggregate-prone proteins in an mTOR-dependent or -independent manner. The mTOR-dependent autophagy inducers, rapamycin and curcumin, directly inhibit mTORC1 activity, resulting in activation of the ULK1 complex. Conversely, mTOR-independent agents upregulate autophagy activity through various intracellular signaling cascade or lysosome biogenesis.
Formal Description Interaction-ID: 145069	drug/chemical compound Rapamycin increases_activity of complex/PPI ULK1 complex via inhibiting mTORC1 activity

Comment	Treatment of various autophagy-inducing agents enhances the clearance of aggregate-prone proteins in an mTOR-dependent or -independent manner. The mTOR-dependent autophagy inducers, rapamycin and curcumin, directly inhibit mTORC1 activity, resulting in activation of the ULK1 complex. Conversely, mTOR-independent agents upregulate autophagy activity through various intracellular signaling cascade or lysosome biogenesis.
Formal Description Interaction-ID: 145073	drug/chemical compound Curcumin increases_activity of complex/PPI ULK1 complex via inhibiting mTORC1 activity

Comment	Treatment of various autophagy-inducing agents enhances the clearance of aggregate-prone proteins in an mTOR-dependent or -independent manner. The mTOR-dependent autophagy inducers, rapamycin and curcumin, directly inhibit mTORC1 activity, resulting in activation of the ULK1 complex. Conversely, mTOR-independent agents upregulate autophagy activity through various intracellular signaling cascade or lysosome biogenesis.
Formal Description Interaction-ID: 145074	complex/PPI mTORC1 complex decreases_activity of complex/PPI ULK1 complex

Comment	Treatment of various autophagy-inducing agents enhances the clearance of aggregate-prone proteins in an mTOR-dependent or -independent manner. The mTOR-dependent autophagy inducers, rapamycin and curcumin, directly inhibit mTORC1 activity, resulting in activation of the ULK1 complex. Conversely, mTOR-independent agents upregulate autophagy activity through various intracellular signaling cascade or lysosome biogenesis.
Formal Description Interaction-ID: 145075	complex/PPI ULK1 complex increases_activity of process autophagy

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145079	drug/chemical compound Verapamil decreases_activity of phenotype mood disorder inducing the degradation of aggregate-prone proteins
Drugbank entries	Show/Hide entries for Verapamil
Drugbank DB00661	Verapamil other SCN5A
Drugbank DB00661	Verapamil inhibitor KCNJ11
Drugbank DB00661	Verapamil inhibitor CACNB4
Drugbank DB00661	Verapamil inhibitor CACNA1G
Drugbank DB00661	Verapamil inhibitor CACNA1F
Drugbank DB00661	Verapamil inhibitor CACNB3
Drugbank DB00661	Verapamil inhibitor CACNA1D
Drugbank DB00661	Verapamil inhibitor CACNB1
Drugbank DB00661	Verapamil inhibitor CACNB2
Drugbank DB00661	Verapamil inhibitor KCNH2
Drugbank DB00661	Verapamil inhibitor CACNA1S
Drugbank DB00661	Verapamil inhibitor CACNA1C
Drugbank DB00661	Verapamil inhibitor CACNA1I
Drugbank DB00661	Verapamil inhibitor CACNA1B
Drugbank DB00661	Verapamil inhibitor CACNA1A
Drugbank DB00661	Verapamil other/unknown SLC6A4

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145080	drug/chemical compound Loperamide decreases_activity of phenotype mood disorder inducing the degradation of aggregate-prone proteins
Drugbank entries	Show/Hide entries for Loperamide
Drugbank DB00836	Loperamide inhibitor CACNA1A
Drugbank DB00836	Loperamide agonist OPRM1
Drugbank DB00836	Loperamide inhibitor CALM1
Drugbank DB00836	Loperamide modulator POMC
Drugbank DB00836	Loperamide agonist OPRD1
Drugbank DB00836	Loperamide agonist OPRK1

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145081	drug/chemical compound Clonidine decreases_activity of phenotype mood disorder inducing the degradation of aggregate-prone proteins
Drugbank entries	Show/Hide entries for Clonidine
Drugbank DB00575	Clonidine agonist ADRA2A
Drugbank DB00575	Clonidine agonist ADRA2B
Drugbank DB00575	Clonidine agonist ADRA2C
Drugbank DB00575	Clonidine agonist ADRA2A

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145082	gene/protein CAST decreases_activity of phenotype mood disorder inducing the degradation of aggregate-prone proteins
Drugbank entries	Show/Hide entries for CAST
Drugbank DB01373	Calcium not specified CAST

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145083	drug/chemical compound Verapamil increases_activity of process autophagy-lysosomal pathway inducing the degradation of aggregate-prone proteins
Drugbank entries	Show/Hide entries for Verapamil
Drugbank DB00661	Verapamil other SCN5A
Drugbank DB00661	Verapamil inhibitor KCNJ11
Drugbank DB00661	Verapamil inhibitor CACNB4
Drugbank DB00661	Verapamil inhibitor CACNA1G
Drugbank DB00661	Verapamil inhibitor CACNA1F
Drugbank DB00661	Verapamil inhibitor CACNB3
Drugbank DB00661	Verapamil inhibitor CACNA1D
Drugbank DB00661	Verapamil inhibitor CACNB1
Drugbank DB00661	Verapamil inhibitor CACNB2
Drugbank DB00661	Verapamil inhibitor KCNH2
Drugbank DB00661	Verapamil inhibitor CACNA1S
Drugbank DB00661	Verapamil inhibitor CACNA1C
Drugbank DB00661	Verapamil inhibitor CACNA1I
Drugbank DB00661	Verapamil inhibitor CACNA1B
Drugbank DB00661	Verapamil inhibitor CACNA1A
Drugbank DB00661	Verapamil other/unknown SLC6A4

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145084	drug/chemical compound Loperamide increases_activity of process autophagy-lysosomal pathway inducing the degradation of aggregate-prone proteins
Drugbank entries	Show/Hide entries for Loperamide
Drugbank DB00836	Loperamide inhibitor CACNA1A
Drugbank DB00836	Loperamide agonist OPRM1
Drugbank DB00836	Loperamide inhibitor CALM1
Drugbank DB00836	Loperamide modulator POMC
Drugbank DB00836	Loperamide agonist OPRD1
Drugbank DB00836	Loperamide agonist OPRK1

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145085	drug/chemical compound Clonidine increases_activity of process autophagy-lysosomal pathway inducing the degradation of aggregate-prone proteins
Drugbank entries	Show/Hide entries for Clonidine
Drugbank DB00575	Clonidine agonist ADRA2A
Drugbank DB00575	Clonidine agonist ADRA2B
Drugbank DB00575	Clonidine agonist ADRA2C
Drugbank DB00575	Clonidine agonist ADRA2A

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145086	gene/protein CAST increases_activity of process autophagy-lysosomal pathway inducing the degradation of aggregate-prone proteins
Drugbank entries	Show/Hide entries for CAST
Drugbank DB01373	Calcium not specified CAST

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145087	process autophagy-lysosomal pathway increases_activity of process degradation of aggregate-prone proteins via reduction in IP3 levels

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145088	drug/chemical compound Verapamil decreases_quantity of drug/chemical compound Inositol 1,4,5-trisphosphate inducing the degradation of aggregate-prone proteins
Drugbank entries	Show/Hide entries for Verapamil
Drugbank DB00661	Verapamil other SCN5A
Drugbank DB00661	Verapamil inhibitor KCNJ11
Drugbank DB00661	Verapamil inhibitor CACNB4
Drugbank DB00661	Verapamil inhibitor CACNA1G
Drugbank DB00661	Verapamil inhibitor CACNA1F
Drugbank DB00661	Verapamil inhibitor CACNB3
Drugbank DB00661	Verapamil inhibitor CACNA1D
Drugbank DB00661	Verapamil inhibitor CACNB1
Drugbank DB00661	Verapamil inhibitor CACNB2
Drugbank DB00661	Verapamil inhibitor KCNH2
Drugbank DB00661	Verapamil inhibitor CACNA1S
Drugbank DB00661	Verapamil inhibitor CACNA1C
Drugbank DB00661	Verapamil inhibitor CACNA1I
Drugbank DB00661	Verapamil inhibitor CACNA1B
Drugbank DB00661	Verapamil inhibitor CACNA1A
Drugbank DB00661	Verapamil other/unknown SLC6A4

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145089	drug/chemical compound Loperamide decreases_quantity of drug/chemical compound Inositol 1,4,5-trisphosphate inducing the degradation of aggregate-prone proteins
Drugbank entries	Show/Hide entries for Loperamide
Drugbank DB00836	Loperamide inhibitor CACNA1A
Drugbank DB00836	Loperamide agonist OPRM1
Drugbank DB00836	Loperamide inhibitor CALM1
Drugbank DB00836	Loperamide modulator POMC
Drugbank DB00836	Loperamide agonist OPRD1
Drugbank DB00836	Loperamide agonist OPRK1

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145090	drug/chemical compound Clonidine decreases_quantity of drug/chemical compound Inositol 1,4,5-trisphosphate inducing the degradation of aggregate-prone proteins
Drugbank entries	Show/Hide entries for Clonidine
Drugbank DB00575	Clonidine agonist ADRA2A
Drugbank DB00575	Clonidine agonist ADRA2B
Drugbank DB00575	Clonidine agonist ADRA2C
Drugbank DB00575	Clonidine agonist ADRA2A

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145091	gene/protein CAST decreases_quantity of drug/chemical compound Inositol 1,4,5-trisphosphate inducing the degradation of aggregate-prone proteins
Drugbank entries	Show/Hide entries for CAST
Drugbank DB01373	Calcium not specified CAST

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145092	drug/chemical compound Inositol 1,4,5-trisphosphate decreases_activity of process autophagosome assembly inducing the degradation of aggregate-prone proteins

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145093	drug/chemical compound Lithium decreases_activity of gene/protein IMPase
Drugbank entries	Show/Hide entries for Lithium
Drugbank DB01356	Lithium inhibitor IMPA2
Drugbank DB01356	Lithium inhibitor IMPA1
Drugbank DB01356	Lithium inhibitor GSK3B
Drugbank DB01356	Lithium inhibitor INPP1
Drugbank DB01356	Lithium potentiator GRIA3

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145094	drug/chemical compound Carbamazepine decreases_activity of process inositol biosynthetic process
Drugbank entries	Show/Hide entries for Carbamazepine
Drugbank DB00564	Carbamazepine inhibitor SCN5A
Drugbank DB00564	Carbamazepine inhibitor SCN5A

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145095	drug/chemical compound Valproic acid decreases_activity of process inositol biosynthetic process
Drugbank entries	Show/Hide entries for Valproic acid
Drugbank DB00313	Valproic Acid inhibitor ABAT
Drugbank DB00313	Valproic Acid inhibitor HDAC9
Drugbank DB00313	Valproic Acid inhibitor ACADSB

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145096	process autophagosome assembly increases_activity of process autophagy-lysosomal pathway inhibited by IP3

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145097	drug/chemical compound Carbamazepine decreases_quantity of drug/chemical compound Inositol via inhibiting inositol synthesis
Drugbank entries	Show/Hide entries for Carbamazepine
Drugbank DB00564	Carbamazepine inhibitor SCN5A
Drugbank DB00564	Carbamazepine inhibitor SCN5A

Comment	Some mood stabilizers, such as verapamil, loperamide, clonidine, and calpastatin, induce the degradation of aggregate-prone proteins by the autophagy-lysosome system via a reduction in inositol phosphate 3 (IP3) levels, which inhibits the autophagosome formation step. In the phosphoinositol cycle, lithium inhibits inositol monophosphatase (IMPase), whereas carbamazepine and valproic acid inhibit inositol synthesis.
Formal Description Interaction-ID: 145098	drug/chemical compound Valproic acid decreases_quantity of drug/chemical compound Inositol via inhibiting inositol synthesis
Drugbank entries	Show/Hide entries for Valproic acid
Drugbank DB00313	Valproic Acid inhibitor ABAT
Drugbank DB00313	Valproic Acid inhibitor HDAC9
Drugbank DB00313	Valproic Acid inhibitor ACADSB

Comment	An autophagy activator, such as rapamycin or trehalose, reduced the number of inclusion bodies.
Formal Description Interaction-ID: 145099	drug/chemical compound Trehalose increases_activity of process autophagy reducing the number of inclusion bodies

Comment	The mTOR-independent autophagy inducer trehalose enhances autophagy by activating AMPK or TFEB.
Formal Description Interaction-ID: 145100	drug/chemical compound Trehalose increases_activity of complex/PPI AMPK mTOR-independent autophagy inducer

Comment	The mTOR-independent autophagy inducer trehalose enhances autophagy by activating AMPK or TFEB.
Formal Description Interaction-ID: 145101	drug/chemical compound Trehalose increases_activity of gene/protein TFEB mTOR-independent autophagy inducer