ReviewThe Journal of biological chemistry2020
The emerging role of α-synuclein truncation in aggregation and disease.
Review in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
109 citing papers in PubMed, 179 citations in OpenAlex.
- Astrocytic cathepsin D promotes α-synuclein processing and Lewy neurite-like aggregate maturation.EMBO reports · 2026Article
- Complement dysregulation during the early phases of synucleinopathy.Acta neuropathologica · 2026Article
- Development of an RNA aptamer as a therapeutic agent for synucleinopathies.Nature communications · 2026Article
- Overexpression of phosphorylated and truncated α-Synuclein does not trigger Parkinsonian readouts in A53T-SNCA mice.NPJ Parkinson's disease · 2026Article
- Structure-function relationship of alpha-synuclein fibrillar polymorphs derived from distinct synucleinopathies.Molecular systems biology · 2026Article
- In silico peptide self-assembly reveals the importance of N-terminal motifs and the inhibition mechanism of the mutation L38M in α-synuclein fibrillation.Protein science : a publication of the Protein Society · 2026Article
- Brain-Only Versus GI-Only Synucleinopathy: A Comprehensive Autopsy Study With Both IHC and SAA.medRxiv : the preprint server for health sciences · 2026Article
- Alpha-Synuclein in Neurodegeneration: From Shared Biology to Disease-Specific Phenotypes.Cells · 2026Review
- α-Synuclein in Lewy Body Diseases: Progress, Remaining Challenges and Future Perspectives.Expert reviews in molecular medicine · 2026Review
- Parkinson's disease-specific α-Synuclein variants potentially drive Lewy body formation by engaging in promiscuous and non-functional interactions.Communications biology · 2026Article
- Internalized SNCA/α-synuclein fibrils become truncated and resist degradation in neurons while glial cells rapidly degrade SNCA fibrils.Autophagy · 2026Article
- Molecular Dynamics Study of α-Synuclein Domain Deletion Mutant Monomers.Biomolecules · 2025Article
- C-terminus-dependent detection of lysosomal alpha-synuclein in nigral Parkinson's disease human brain neurons.Molecular neurodegeneration · 2025Article
- ZnJournal of the American Chemical Society · 2025Article
- "Coordination of Anle138b to Silver Results in Selective Reduction of a C-terminal truncated Alpha-synuclein Protein and Increased Aggregate Size."bioRxiv : the preprint server for biology · 2025Article
- Lysine-Targeting Inhibitors of Amyloidogenic Protein Aggregation: A Promise for Neurodegenerative Proteinopathies.JACS Au · 2025Review
- Alpha-synuclein interacts with regulators of ATP homeostasis in mitochondria.Nature communications · 2025Article
- Seed Amplification Assay for α-Synuclein: Diagnostic Applications in Synucleinopathies.International journal of molecular sciences · 2025Review
- Synaptic enrichment of pSer129 alpha-synuclein correlates with dopaminergic denervation in early-stage Parkinson's disease.Nature communications · 2025Article
- Effect of RNA on the supramolecular architecture of α-synuclein fibrils.Biophysical journal · 2025Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
α-Synuclein (αsyn) is an abundant brain neuronal protein that can misfold and polymerize to form toxic fibrils coalescing into pathologic inclusions in neurodegenerative diseases, including Parkinson's disease, Lewy body dementia, and multiple system atrophy. These fibrils may induce further αsyn misfolding and propagation of pathologic fibrils in a prion-like process. It is unclear why αsyn initially misfolds, but a growing body of literature suggests a critical role of partial proteolytic processing resulting in various truncations of the highly charged and flexible carboxyl-terminal region. This review aims to 1) summarize recent evidence that disease-specific proteolytic truncations of αsyn occur in Parkinson's disease, Lewy body dementia, and multiple system atrophy and animal disease models; 2) provide mechanistic insights on how truncation of the amino and carboxyl regions of αsyn may modulate the propensity of αsyn to pathologically misfold; 3) compare experiments evaluating the prion-like properties of truncated forms of αsyn in various models with implications for disease progression; 4) assess uniquely toxic properties imparted to αsyn upon truncation; and 5) discuss pathways through which truncated αsyn forms and therapies targeted to interrupt them. Cumulatively, it is evident that truncation of αsyn, particularly carboxyl truncation that can be augmented by dysfunctional proteostasis, dramatically potentiates the propensity of αsyn to pathologically misfold into uniquely toxic fibrils with modulated prion-like seeding activity. Therapeutic strategies and experimental paradigms should operate under the assumption that truncation of αsyn is likely occurring in both initial and progressive disease stages, and preventing truncation may be an effective preventative strategy against pathologic inclusion formation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.