ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience1999
alpha-Synuclein shares physical and functional homology with 14-3-3 proteins.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
181 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-analysis and in-silico functional characterization of the SNCA variant rs356220 in Parkinson's disease.Scientific reports · 2025Pooled it
- 14-3-3σ up-regulation in the temporal cortex associates with tau pathology and reactive astroglia in Lewy body disorders.Brain pathology (Zurich, Switzerland) · 2026Article
- Heat shock protein 10 as a chaperone modulating α-synuclein amyloid fibril formation.Protein science : a publication of the Protein Society · 2026Article
- The Role of LVV-H7 in Alcohol-Induced Reward Mechanisms.Addiction biology · 2025Article
- A novel 14-3-3θ phosphomimetic mouse model demonstrates social dominance defects.Biology open · 2025Article
- Article
- Identification of Candidate Protein Biomarkers Associated with Domoic Acid Toxicosis in Cerebrospinal Fluid of California Sea Lions (Journal of proteome research · 2024Article
- A-Syn(ful) MAM: A Fresh Perspective on a Converging Domain in Parkinson's Disease.International journal of molecular sciences · 2024Review
- Altered TFEB subcellular localization in nigral neurons of subjects with incidental, sporadic and GBA-related Lewy body diseases.Acta neuropathologica · 2024Article
- Mutant α-synuclein causes death of human cortical neurons via ERK1/2 and JNK activation.Molecular brain · 2024Article
- Formation of amyloid fibrils by the regulatory 14-3-3Open biology · 2024Article
- 14-3-3 proteins-a moonlight protein complex with therapeutic potential in neurological disorder: in-depth review with Alzheimer's disease.Frontiers in molecular biosciences · 2024Review
- Alpha-Synuclein Contribution to Neuronal and Glial Damage in Parkinson's Disease.International journal of molecular sciences · 2023Review
- The post-translational regulation of transcription factor EB (TFEB) in health and disease.EMBO reports · 2023Review
- GM1 oligosaccharide efficacy against α-synuclein aggregation and toxicity in vitro.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023Article
- Autophagy and autophagy-related molecules in neurodegenerative diseases.Animal models and experimental medicine · 2023Review
- Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders.Frontiers in molecular neuroscience · 2023Review
- Concomitant protein pathogenesis in Parkinson's disease and perspective mechanisms.Frontiers in aging neuroscience · 2023Review
- Structural insights into the functional roles of 14-3-3 proteins.Frontiers in molecular biosciences · 2022Review
- The Amyloid Fibril-Forming β-Sheet Regions of Amyloid β and α-Synuclein Preferentially Interact with the Molecular Chaperone 14-3-3ζ.Molecules (Basel, Switzerland) · 2021Article
121 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
alpha-Synuclein has been implicated in the pathophysiology of many neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease. Mutations in alpha-synuclein cause some cases of familial PD (Polymeropoulos et al., 1997; Kruger et al., 1998). In addition, many neurodegenerative diseases show accumulation of alpha-synuclein in dystrophic neurites and in Lewy bodies (Spillantini et al., 1998). Here, we show that alpha-synuclein shares physical and functional homology with 14-3-3 proteins, which are a family of ubiquitous cytoplasmic chaperones. Regions of alpha-synuclein and 14-3-3 proteins share over 40% homology. In addition, alpha-synuclein binds to 14-3-3 proteins, as well as some proteins known to associate with 14-3-3, including protein kinase C, BAD, and extracellular regulated kinase, but not Raf-1. We also show that overexpression of alpha-synuclein inhibits protein kinase C activity. The association of alpha-synuclein with BAD and inhibition of protein kinase C suggests that increased expression of alpha-synuclein could be harmful. Consistent with this hypothesis, we observed that overexpression of wild-type alpha-synuclein is toxic, and overexpression of alpha-synuclein containing the A53T or A30P mutations exhibits even greater toxicity. The activity and binding profile of alpha-synuclein suggests that it might act as a protein chaperone and that accumulation of alpha-synuclein could contribute to cell death in neurodegenerative diseases.
Indexed as
Identifiers
10407019PMC6783081What OpenQuestion holds
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.