Gaucher disease - more than just a rare lipid storage disease.
Extracellular vesicles
Gaucher disease
Glycosphingolipids
Inflammation
Lysosomal storage disease
Oxidative stress
Journal
Journal of molecular medicine (Berlin, Germany)
ISSN: 1432-1440
Titre abrégé: J Mol Med (Berl)
Pays: Germany
ID NLM: 9504370
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
01
07
2021
accepted:
06
12
2021
revised:
29
10
2021
pubmed:
24
1
2022
medline:
11
5
2022
entrez:
23
1
2022
Statut:
ppublish
Résumé
Gaucher disease (GD), one of the most common lysosomal storage diseases, is caused by mutations in the gene, GBA1, that leads to defective glucocerebrosidase activity resulting in the accumulation and storage of glycosphingolipids. However, the pathophysiology of GD is more complicated leading to various associated conditions such as skeletal manifestations and Parkinson's disease (PD). These may result from oxidative stress and inflammatory responses due to complex interconnection of downstream factors such as substrate accumulation, endoplasmic reticulum (ER) stress, unfolded protein response (UPR), calcium dysregulation, mitochondrial dysfunction, defective autophagy, accumulation of α-synuclein aggregates, altered secretion and function of extracellular vesicles (EVs), and immunologic hyperactivity. Here we provide an overview of lysosomal storage diseases followed by a comprehensive review of the factors contributing to oxidative stress and inflammation in GD pathophysiology, mechanisms underlying the possible associated complications, current established treatments for GD, their limitations, and potential primary and adjunctive treatment options targeting these factors.
Identifiants
pubmed: 35066608
doi: 10.1007/s00109-021-02174-z
pii: 10.1007/s00109-021-02174-z
doi:
Substances chimiques
Lipids
0
alpha-Synuclein
0
Glucosylceramidase
EC 3.2.1.45
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
499-518Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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