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Neurodegenerative Diseases: Expanding the Prion Concept
Open accessAbstract
The prion paradigm has emerged as a unifying molecular principle for the pathogenesis of many age-related neurodegenerative diseases. This paradigm holds that a fundamental cause of specific disorders is the misfolding and seeded aggregation of certain proteins. The concept arose from the discovery that devastating brain diseases called spongiform encephalopathies are transmissible to new hosts by agents consisting solely of a misfolded protein, now known as the prion protein. Accordingly, “prion” was defined as a “proteinaceous infectious particle.” As the concept has expanded to include other diseases, many of which are not infectious by any conventional definition, the designation of prions as infectious agents has become problematic. We propose to define prions as “proteinaceous nucleating particles” to highlight the molecular action of the agents, lessen unwarranted apprehension about the transmissibility of noninfectious proteopathies, and promote the wider acceptance of this revolutionary paradigm by the biomedical community.
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“The prion paradigm has been expanded to many neurodegenerative diseases, including Alzheimer disease (AD), Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and others (94).”
From Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017) · cites this paper as [94]
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“Aβ fibrillization can be “seeded” in a prion-like manner by the presence of small assemblies of misfolded beta-sheet-containing Aβ seeds that template the formation of larger amyloid aggregates”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Walker and Jucker, 2015
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Metadata
- Authors
- Walker, L. C., & Jucker, M.
- Affiliations
- Emory University (US)
- German Center for Neurodegenerative Diseases (DE)
- Venue
- Annual Review of Neuroscience
- Publisher
- Annual Reviews
- Published
- 2015-07-08
- Volume
- 38
- Issue
- 1
- Pages
- 87-103
- ISSN
- 0147-006X (ISSN-L)
- 1545-4126
- PMC
- PMC4803040
- OpenAlex
- W2156606243
- Cited by
- 361
- References
- 174
- Citations by year
- 2026: 18 · 2025: 21 · 2024: 24 · 2023: 22 · 2022: 34 · 2021: 26 · 2020: 48 · 2019: 34 · 2018: 39 · 2017: 40 · 2016: 42 · 2015: 13
- FWCI
- 4.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DZNE Pub (submittedVersion)
- Funders
- MetLife Foundation
- Bundesministerium für Bildung und Forschung (01GI0705)
- National Institutes of Health (RR000165, AG025688, OD11132, P51OD011132)
- National Institute on Aging (AG 025688, R21AG040589, P50AG025688, AG040589)
- National Center for Research Resources (RR000165, P51RR000165)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- neurodegenerative diseases, protein misfolding, seeded aggregation, spongiform encephalopathy, prion protein, proteinopathies, transmissibility, age-related neurodegeneration, pathogenesis
- MeSH terms
- Animals, Humans, Prions, Neurodegenerative Diseases
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