Neurodegeneration and aging pathways in Mucopolysaccharidosis IIIB

Mucopolysaccharidosis type IIIB (MPS IIIB), or Sanfilippo Syndrome type B, is a lysosomal storage disorder caused by mutations in the NAGLU gene, which encodes the enzyme alpha-N-acetylglucosaminidase, responsible for the degradation of heparan sulfate. Progressive accumulation of undegraded glycosa...

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Main Author: Yorran Hardman Araújo Montenegro
Format: Article
Language:English
Published: Open Exploration Publishing Inc. 2025-07-01
Series:Exploration of Neuroscience
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Online Access:https://www.explorationpub.com/uploads/Article/A1006103/1006103.pdf
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author Yorran Hardman Araújo Montenegro
author_facet Yorran Hardman Araújo Montenegro
author_sort Yorran Hardman Araújo Montenegro
collection DOAJ
description Mucopolysaccharidosis type IIIB (MPS IIIB), or Sanfilippo Syndrome type B, is a lysosomal storage disorder caused by mutations in the NAGLU gene, which encodes the enzyme alpha-N-acetylglucosaminidase, responsible for the degradation of heparan sulfate. Progressive accumulation of undegraded glycosaminoglycans primarily affects the central nervous system, resulting in severe neurodegeneration. Cellular findings reveal impaired intracellular trafficking, especially within the Golgi apparatus, linked to GM130 depletion and accumulation of GM2 and GM3 gangliosides. Endocytic vesicles fail to properly fuse with lysosomes due to genetic defects, disrupting lysosomal degradation. This contributes to oxidative stress, mitochondrial dysfunction, and mitophagy failure, which collectively drive neuronal apoptosis. MPS IIIB shares pathways with Alzheimer’s and Parkinson’s, suggesting cellular aging processes. Given the lack of specific treatment, modulation of inflammatory pathways such as TLR4 emerges as a potential therapeutic strategy.
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spelling doaj-art-7cc2e72e1aeb44a089514ff69a8e22b72025-08-20T03:34:09ZengOpen Exploration Publishing Inc.Exploration of Neuroscience2834-53472025-07-014100610310.37349/en.2025.1006103Neurodegeneration and aging pathways in Mucopolysaccharidosis IIIBYorran Hardman Araújo Montenegro0https://orcid.org/0000-0002-0684-1818MPS Brazil Network, Hospital de Clínicas de Porto Alegre, Porto Alegre 90410-000, BrazilMucopolysaccharidosis type IIIB (MPS IIIB), or Sanfilippo Syndrome type B, is a lysosomal storage disorder caused by mutations in the NAGLU gene, which encodes the enzyme alpha-N-acetylglucosaminidase, responsible for the degradation of heparan sulfate. Progressive accumulation of undegraded glycosaminoglycans primarily affects the central nervous system, resulting in severe neurodegeneration. Cellular findings reveal impaired intracellular trafficking, especially within the Golgi apparatus, linked to GM130 depletion and accumulation of GM2 and GM3 gangliosides. Endocytic vesicles fail to properly fuse with lysosomes due to genetic defects, disrupting lysosomal degradation. This contributes to oxidative stress, mitochondrial dysfunction, and mitophagy failure, which collectively drive neuronal apoptosis. MPS IIIB shares pathways with Alzheimer’s and Parkinson’s, suggesting cellular aging processes. Given the lack of specific treatment, modulation of inflammatory pathways such as TLR4 emerges as a potential therapeutic strategy.https://www.explorationpub.com/uploads/Article/A1006103/1006103.pdfmucopolysaccharidosis iiibneuronal agingcellular senescenceneurodegeneration
spellingShingle Yorran Hardman Araújo Montenegro
Neurodegeneration and aging pathways in Mucopolysaccharidosis IIIB
Exploration of Neuroscience
mucopolysaccharidosis iiib
neuronal aging
cellular senescence
neurodegeneration
title Neurodegeneration and aging pathways in Mucopolysaccharidosis IIIB
title_full Neurodegeneration and aging pathways in Mucopolysaccharidosis IIIB
title_fullStr Neurodegeneration and aging pathways in Mucopolysaccharidosis IIIB
title_full_unstemmed Neurodegeneration and aging pathways in Mucopolysaccharidosis IIIB
title_short Neurodegeneration and aging pathways in Mucopolysaccharidosis IIIB
title_sort neurodegeneration and aging pathways in mucopolysaccharidosis iiib
topic mucopolysaccharidosis iiib
neuronal aging
cellular senescence
neurodegeneration
url https://www.explorationpub.com/uploads/Article/A1006103/1006103.pdf
work_keys_str_mv AT yorranhardmanaraujomontenegro neurodegenerationandagingpathwaysinmucopolysaccharidosisiiib