ArticleThe Journal of biological chemistry2011
Hsc70 protein interaction with soluble and fibrillar alpha-synuclein.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Brain DNA methylomic analysis of frontotemporal lobar degeneration reveals OTUD4 in shared dysregulated signatures across pathological subtypes.Acta neuropathologica · 2023Pooled it
- Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Polyamine metabolic enzyme SAT1 remodels the neuronal transcriptome and rescues α-synuclein toxicity in Drosophila.Amino acids · 2026Article
- Disruption of Synaptic Vesicle Trafficking in Alzheimer's and Parkinson's Disease: Mechanisms and Therapeutic Implication.International journal of molecular sciences · 2026Review
- Polyamine metabolic enzyme SAT1 remodels the neuronal transcriptome and rescues α-synuclein toxicity in Drosophila.Research square · 2026Article
- Plasma α-synuclein and QSM-derived susceptibility in Parkinson's disease: associations with clinical features.Frontiers in aging neuroscience · 2026Article
- Synaptic Chaperone Dysfunction as a Convergent Mechanism in Neurodegenerative and Psychiatric Disorders.Neuroscience insights · 2026Review
- Controlling interfacial protein adsorption, desorption and aggregation in biomolecular condensates.Nature communications · 2025Article
- DnaJB1 chaperone inhibits tau aggregation by recognizing its N-terminus.bioRxiv : the preprint server for biology · 2025Article
- Competing chaperone pathways in α-synuclein disaggregation and aggregation dynamics.Protein science : a publication of the Protein Society · 2025Article
- Dysregulated ac4C modification of mRNA in a mouse model of early-stage Alzheimer's disease.Cell & bioscience · 2025Article
- Article
- Mutant mice with rod-specific VPS35 deletion exhibit retinal α-synuclein pathology-associated degeneration.Nature communications · 2024Article
- Aberrant CHCHD2-associated mitochondriopathy in Kii ALS/PDC astrocytes.Acta neuropathologica · 2024Article
- NGLY1 mutations cause protein aggregation in human neurons.Cell reports · 2023Article
- α-Synuclein oligomers and fibrils: partners in crime in synucleinopathies.Neural regeneration research · 2023Article
- The roles of HSP40/DNAJ protein family in neurodegenerative diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Review
- Genetic Analysis of HSP40/DNAJ Family Genes in Parkinson's Disease: a Large Case-Control Study.Molecular neurobiology · 2022Article
- Effects of oligomer toxicity, fibril toxicity and fibril spreading in synucleinopathies.Cellular and molecular life sciences : CMLS · 2022Review
- Regulation by Different Types of Chaperones of Amyloid Transformation of Proteins Involved in the Development of Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aggregation of α-synuclein (α-Syn), the primary component of Lewy bodies, into high molecular weight assemblies is strongly associated with Parkinson disease. This event is believed to result from a conformational change within native α-Syn. Molecular chaperones exert critical housekeeping functions in vivo including refolding, maintaining in a soluble state, and/or pacifying protein aggregates. The influence of the stress-induced heat shock protein 70 (Hsp70) on α-Syn aggregation has been notably investigated. The constitutively expressed chaperone Hsc70 acts as an antiaggregation barrier before cells are overwhelmed with α-Syn aggregates and Hsp70 expression induced. Here, we investigate the interaction between Hsc70 and α-Syn, the consequences of this interaction, and the role of nucleotides and co-chaperones Hdj1 and Hdj2 as modulators. We show that Hsc70 sequesters soluble α-Syn in an assembly incompetent complex in the absence of ATP. The affinity of Hsc70 for soluble α-Syn diminishes upon addition of ATP alone or together with its co-chaperones Hdj1 or Hdj2 allowing faster binding and release of client proteins thus abolishing α-Syn assembly inhibition by Hsc70. We show that Hsc70 binds α-Syn fibrils with a 5-fold tighter affinity compared with soluble α-Syn. This suggests that Hsc70 preferentially interacts with high molecular weight α-Syn assemblies in vivo. Hsc70 binding certainly has an impact on the physicochemical properties of α-Syn assemblies. We show a reduced cellular toxicity of α-Syn fibrils coated with Hsc70 compared with "naked" fibrils. Hsc70 may therefore significantly affect the cellular propagation of α-Syn aggregates and their spread throughout the central nervous system in Parkinson disease.
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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.