N-acetyl-alpha-glucosaminidase (NAGLU) (NAGLU)

N-acetyl-alpha-glucosaminidase (NAGLU) is a lysosomal enzyme essential for the degradation of heparan sulfate, a glycosaminoglycan found in the extracellular matrix and on cell surfaces (UniProt: P54802). The enzyme specifically catalyzes the hydrolysis of terminal N-acetyl-D-glucosamine residues that are alpha-linked to the non-reducing end of heparan sulfate (NCBI Gene: 4669). Mutations in the NAGLU gene result in a deficiency of this enzyme, leading to Mucopolysaccharidosis type IIIB (MPS IIIB), also known as Sanfilippo syndrome type B (OMIM: 252920). This lysosomal storage disorder is characterized by the progressive accumulation of heparan sulfate, which is particularly damaging to the central nervous system, causing severe neurodegeneration, cognitive impairment, and behavioral disturbances (PubMed: 29127305). Therapeutic approaches targeting NAGLU include enzyme replacement therapies (ERT) like Tralesinidase alfa and gene therapies such as ABO-101 and LYS-SAF302, which aim to restore functional enzyme levels (ClinicalTrials.gov: NCT03315182). A major challenge in treating MPS IIIB is ensuring the enzyme or gene delivery system effectively crosses the blood-brain barrier to address the primary neurological symptoms.

Other names

Alpha-N-acetylglucosaminidaseNAGSanfilippo B protein

Enzyme replacement therapy (ERT) provides a functional version of the enzyme to the lysosomes, while gene therapy (gene augmentation) introduces a functional copy of the NAGLU gene to restore endogenous enzyme production.