Cited by 136Parkinson's Disease Mechanisms and TreatmentsAlzheimer's disease research and treatmentsNuclear Receptors and Signaling

Alpha-Synuclein: Mechanisms of Release and Pathology Progression in Synucleinopathies

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Brás, Inês C., Outeiro, Tiago F.·2021·Cells

Abstract

The accumulation of misfolded alpha-synuclein (aSyn) throughout the brain, as Lewy pathology, is a phenomenon central to Parkinson’s disease (PD) pathogenesis. The stereotypical distribution and evolution of the pathology during disease is often attributed to the cell-to-cell transmission of aSyn between interconnected brain regions. The spreading of conformationally distinct aSyn protein assemblies, commonly referred as strains, is thought to result in a variety of clinically and pathologically heterogenous diseases known as synucleinopathies. Although tremendous progress has been made in the field, the mechanisms involved in the transfer of these assemblies between interconnected neural networks and their role in driving PD progression are still unclear. Here, we present an update of the relevant discoveries supporting or challenging the prion-like spreading hypothesis. We also discuss the importance of aSyn strains in pathology progression and the various putative molecular mechanisms involved in cell-to-cell protein release. Understanding the pathways underlying aSyn propagation will contribute to determining the etiology of PD and related synucleinopathies but also assist in the development of new therapeutic strategies.

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Authors
Brás, I. C., & Outeiro, T. F.
Affiliations
  • Universitätsmedizin Göttingen (DE)
  • German Center for Neurodegenerative Diseases (DE)
Corresponding author
Outeiro, Tiago F.
Venue
Cells
Publisher
MDPI AG
Published
2021-02-12
Volume
10
Issue
2
Pages
375
ISSN
2073-4409 (ISSN-L)
OpenAlex
W3130859323
Cited by
136
References
209
Citations by year
2026: 20 · 2025: 32 · 2024: 32 · 2023: 22 · 2022: 18 · 2021: 12
FWCI
2.69
Type
journal article
Language
en
Open access
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DZNE Pub (submittedVersion, cc-by)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
  • Newcastle University ePrints (Newcastle Univesity) (cc-by)
Funders
Deutsche Forschungsgemeinschaft (MBExC)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
alpha-synuclein, synucleinopathies, Parkinson's disease, Lewy body pathology, prion-like spreading, protein misfolding
MeSH terms
Synucleinopathies, Brain, Humans, Parkinson Disease, Prions, Disease Progression, alpha-Synuclein

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