Cited by 21Parkinson's Disease Mechanisms and TreatmentsHeat shock proteins researchAlzheimer's disease research and treatments

The Neuroprotective Role of Protein Quality Control in Halting the Development of Alpha-Synuclein Pathology

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Manecka, Destiny-Love, Vanderperre, Benoît, Fon, Edward A., Durcan, Thomas M.·2017·Frontiers in Molecular Neuroscience

Abstract

Synucleinopathies are a family of neurodegenerative disorders that comprises Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Each of these disorders is characterized by devastating motor, cognitive, and autonomic consequences. Current treatments for synucleinopathies are not curative and are limited to improvement of quality of life for affected individuals. Although the underlying causes of these diseases are unknown, a shared pathological hallmark is the presence of proteinaceous inclusions containing the α-synuclein (α-syn) protein in brain tissue. In the past few years, it has been proposed that these inclusions arise from the self-templated, prion-like spreading of misfolded and aggregated forms of α-syn throughout the brain, leading to neuronal dysfunction and death. In this review, we describe how impaired protein homeostasis is a prominent factor in the α-syn aggregation cascade, with alterations in protein quality control (PQC) pathways observed in the brains of patients. We discuss how PQC modulates α-syn accumulation, misfolding and aggregation primarily through chaperoning activity, proteasomal degradation, and lysosome-mediated degradation. Finally, we provide an overview of experimental data indicating that targeting PQC pathways is a promising avenue to explore in the design of novel neuroprotective approaches that could impede the spreading of α-syn pathology and thus provide a curative treatment for synucleinopathies.

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Authors
Manecka, D.-L., Vanderperre, B., Fon, E. A., & Durcan, T. M.
Affiliations
Montreal Neurological Institute and Hospital (CA)
Corresponding author
Durcan, Thomas M.
Venue
Frontiers in Molecular Neuroscience
Published
2017-09-27
Volume
10
Pages
311-311
ISSN
1662-5099 (ISSN-L)
OpenAlex
W2760459282
Cited by
21
References
161
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 3
FWCI
0.40
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship@McGill (McGill) (submittedVersion)
  • eScholarship@McGill (McGill) (submittedVersion, cc-by)
Funders
  • Michael J. Fox Foundation for Parkinson’s Research (12241)
  • Canadian Institutes of Health Research (MFE 152571)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
protein quality control, alpha-synuclein, synucleinopathies, Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, protein aggregation, prion-like spreading, proteostasis, molecular chaperones, proteasomal degradation, lysosomal degradation, neuroprotection, neurodegeneration

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