General Information:

Id: 8,418
Diseases: Metabolic
Mus musculus
article/cited
Reference: Urayama A et al.(2008) Mannose 6-phosphate receptor-mediated transport of sulfamidase across the blood-brain barrier in the newborn mouse Mol. Ther. 16: 1261-1266 [PMID: 18443601]

Interaction Information:

Comment Mucopolysaccharidosis type IIIA (MPS IIIA), which is a lysosomal storage disorder (LSD) caused by inherited deficiency of sulfamidase, is characterized by severe, progressive central nervous system (CNS) dysfunction. Enzyme replacement therapy (ERT) to treat CNS storage is challenging, because the access of enzymes to the brain is restricted by the blood-brain barrier (BBB). (cited information)
Formal Description
Interaction-ID: 85699

gene/protein

SGSH

affects_activity of

disease

Mucopolysaccharidosis type IIIA

Comment Recombinant human sulfamidase crosses the neonatal BBB through the M6P/IGF2 receptor‚Äďmediated transcytosis pathway, a transporter it shares with phosphorylated beta-glucuronidase (P-GUS). Capillary depletion revealed that 83.7% of the sulfamidase taken up by the brain was in the parenchyma, demonstrating transfer across the capillary wall.
Formal Description
Interaction-ID: 85700

gene/protein

IGF2R

increases_transport of

gene/protein

SGSH

through BBB (blood-brain barrier) to the parenchyma; through the M6P/IGF2 receptor‚Äďmediated transcytosis pathway
Drugbank entries Show/Hide entries for IGF2R
Comment The uptake of sulfamidase into the brain was significantly reduced by co-injections of M6P and P-GUS. That is, the transport of sulfamidase into the brain parenchyma in early postnatal life is mediated by the M6P receptor, which is shared with P-GUS and is likely accessible to other M6P-containing lysosomal enzymes.
Formal Description
Interaction-ID: 85702

drug/chemical compound

D-Mannose 6-phosphate

decreases transport of

gene/protein

SGSH

through BBB (blood-brain barrier)
Comment Mucopolysaccharidosis type IIIA (MPS IIIA), which is a lysosomal storage disorder (LSD) caused by inherited deficiency of sulfamidase, is characterized by severe, progressive central nervous system (CNS) dysfunction. Enzyme replacement therapy (ERT) to treat CNS storage is challenging, because the access of enzymes to the brain is restricted by the blood-brain barrier (BBB). (cited information)
Formal Description
Interaction-ID: 85703

disease

Mucopolysaccharidosis type IIIA

increases_activity of

phenotype

CNS dysfunction

Comment Sulfamidase is taken up by receptor-mediated endocytosis through the mannose 6-phosphate/insulin-like growth factor 2 (M6P/IGF2) receptor, and prevents lysosomal storage in vitro. Intracerebral injection of sulfamidase into the brains of adult rodents reduces lysosomal storage in the CNS. (cited information)
Formal Description
Interaction-ID: 85704

gene/protein

SGSH

decreases_activity of

disease

Lysosomal storage disease

in vitro; by receptor-mediated endocytosis through the mannose 6-phosphate/insulin-like growth factor 2 (M6P/IGF2) receptor; thus preventing lysosomal storage; enzyme replacement therapy (ERT) is effective only if begun at birth. (cited information)
Comment Recombinant human sulfamidase crosses the neonatal BBB through the M6P/IGF2 receptor‚Äďmediated transcytosis pathway, a transporter it shares with phosphorylated beta-glucuronidase (P-GUS).
Formal Description
Interaction-ID: 85706

gene/protein

IGF2R

increases_activity of

process

transcytosis

through BBB (blood-brain barrier); of sulfamidase
Drugbank entries Show/Hide entries for IGF2R
Comment The uptake of sulfamidase into the brain was significantly reduced by co-injections of M6P and P-GUS (phosphorylated beta-glucuronidase). That is, the transport of sulfamidase into the brain parenchyma in early postnatal life is mediated by the M6P receptor, which is shared with P-GUS and is likely accessible to other M6P-containing lysosomal enzymes.
Formal Description
Interaction-ID: 85707

gene/protein

GUSB

decreases transport of

gene/protein

SGSH

through BBB (blood-brain barrier) to the parenchyma; if GUS is phosphorylated (P-GUS)
Drugbank entries Show/Hide entries for GUSB
Comment Sulfamidase (N-sulfoglucosamine sulfohydrolase; EC 3.10.1.1) cleaves N-linked sulfates from nonreducing terminals of heparan sulfates. The native enzyme forms a 115 kd dimer, composed of two 62 kd monomers, 1,2 each with five N-glycosylation sites.
Formal Description
Interaction-ID: 85708

gene/protein

SGSH

is_part_of

complex/PPI

Sulfamidase

The native enzyme forms a 115 kd dimer, composed of two 62 kd monomers.
Comment Mucopolysaccharidosis type IIIA (MPS IIIA), which is a lysosomal storage disorder (LSD) caused by inherited deficiency of sulfamidase, is characterized by severe, progressive central nervous system (CNS) dysfunction. Enzyme replacement therapy (ERT) to treat CNS storage is challenging, because the access of enzymes to the brain is restricted by the blood-brain barrier (BBB). (cited information)
Formal Description
Interaction-ID: 85709

gene/protein mutant

SGSH-mut

increases_activity of

disease

Mucopolysaccharidosis type IIIA

Comment Sulfamidase (N-sulfoglucosamine sulfohydrolase; EC 3.10.1.1) cleaves N-linked sulfates from nonreducing terminals of heparan sulfates. The native enzyme forms a 115 kd dimer, composed of two 62 kd monomers, 1,2 each with five N-glycosylation sites.
Formal Description
Interaction-ID: 85710

complex/PPI

Sulfamidase

decreases_quantity of

drug/chemical compound

Heparan sulfate

via cleaving N-linked sulfates from nonreducing terminals of heparan sulfates