Journal
FEBS LETTERS
Volume 592, Issue 23, Pages 3806-3818Publisher
WILEY
DOI: 10.1002/1873-3468.13082
Keywords
Alzheimer's disease; heparan sulfates; neurodegeneration; Parkinson's disease; prion diseases; protein aggregation
Funding
- Fondation Vaincre Alzheimer [FR-15055]
- European Union FET OPEN RIA H2020 program [737390]
- GDR GAGoSciences [3739]
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Neurodegenerative disorders, such as Alzheimer's, Parkinson's, and prion diseases, are directly linked to the formation and accumulation of protein aggregates in the brain. These aggregates, principally made of proteins or peptides that clamp together after acquisition of beta-folded structures, also contain heparan sulfates. Several lines of evidence suggest that heparan sulfates centrally participate in the protein aggregation process. In vitro, they trigger misfolding, oligomerization, and fibrillation of amyloidogenic proteins, such as A beta, tau, alpha-synuclein, prion protein, etc. They participate in the stabilization of protein aggregates, protect them from proteolysis, and act as cell-surface receptors for the cellular uptake of proteopathic seeds during their spreading. This review focuses attention on the importance of heparan sulfates in protein aggregation in brain disorders including Alzheimer's, Parkinson's, and prion diseases. The presence of these sulfated polysaccharides in protein inclusions in vivo and their capacity to trigger protein aggregation in vitro strongly suggest that they might play critical roles in the neurodegenerative process. Further advances in glyco-neurobiology will improve our understanding of the molecular and cellular mechanisms leading to protein aggregation and neurodegeneration.
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