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Cited by 183Parkinson's Disease Mechanisms and TreatmentsAlzheimer's disease research and treatmentsNuclear Receptors and Signaling

The concept of alpha-synuclein as a prion-like protein: ten years after

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Steiner, Jennifer A., Quansah, Emmanuel, Brundin, Patrik·2018·Cell and Tissue Research
DOI 10.1007/s00441-018-2814-1PMC PMC6541204
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Abstract

Parkinson's disease is characterized by the loss of nigrostriatal dopaminergic signaling and the presence of alpha-synuclein aggregates (also called Lewy bodies and neurites) throughout the brain. In 2003, Braak and colleagues created a staging system for Parkinson's disease describing the connection between the alpha-synuclein pathology and disease severity. Later, they suggested that the pathology might initially be triggered by exogenous insults targeting the gut and olfactory system. In 2008, we and other groups documented Lewy pathology in grafted neurons in people with Parkinson's disease who had been transplanted over a decade prior to autopsy. We proposed that the Lewy pathology in the grafted neurons was the result of permissive templating or prion-like spread of alpha-synuclein pathology from neurons in the host to those in the grafts. During the following ten years, several studies described the transmission of alpha-synuclein pathology between neurons, both in cell culture and in experimental animals. Recent research has also begun to identify underlying molecular mechanisms. Collectively, these experimental studies tentatively support the idea that the progression from one Braak stage to the next is the consequence of prion-like propagation of Lewy pathology. However, definitive proof that intercellular propagation of alpha-synuclein pathology occurs in Parkinson's disease cases has proven difficult to secure. In this review, we highlight several open questions that currently prevent us from concluding with certainty that prion-like transfer of alpha-synuclein contributes to the progression of Parkinson's disease.

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  • In 2008, Steiner et al. documented α-synuclein Lewy body pathology in grafted neurons in people with PD who had been transplanted over a decade prior to autopsy.

    “In 2008, Steiner et al. documented α-synuclein Lewy body pathology in grafted neurons in people with PD who had been transplanted over a decade prior to autopsy.”

    From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [79]

    The Introduction reports that 2008 transplantation studies found Lewy pathology at autopsy in grafted neurons of people with Parkinson’s disease. But it identifies Kordower et al. and Li et al. as the studies that made the discovery; the cited Steiner et al. paper is a 2018 review, not the 2008 report. No page number is provided for the passage. (LLM, conf=0.86)

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Authors
Steiner, J. A., Quansah, E., & Brundin, P.
Affiliations
Van Andel Institute (US)
Corresponding author
Steiner, Jennifer A.
ORCID
Venue
Cell and Tissue Research
Publisher
Springer Science and Business Media LLC
Published
2018-02-26
Volume
373
Issue
1
Pages
161-173
ISSN
  • 0302-766X (ISSN-L)
  • 1432-0878
DOI
10.1007/s00441-018-2814-1
PMC
PMC6541204
OpenAlex
W2792619350
Cited by
183
References
146
Citations by year
2026: 7 · 2025: 15 · 2024: 26 · 2023: 17 · 2022: 28 · 2021: 27 · 2020: 20 · 2019: 31 · 2018: 12
FWCI
3.55
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Cell and Tissue Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Michael J. Fox Foundation for Parkinson's Research
  • Van Andel Research Institute
  • Teva Pharmaceutical Industries
  • National Institute on Deafness and Other Communication Disorders (R01DC016519)
  • National Institute of Neurological Disorders and Stroke (R21NS105436, R21NS093993)
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, prion-like propagation, Parkinson's disease, Lewy bodies, Braak staging, neurodegeneration
MeSH terms
Animals, Humans, Neurons, Parkinson Disease, Prions, alpha-Synuclein, Connectome, Protein Aggregates

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