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Literature DB >> 22482021

The interaction of Hsc70 protein with fibrillar α-Synuclein and its therapeutic potential in Parkinson's disease.

Abstract

We recently described the effect of the constitutively expressed chaperone, Hsc70 protein, on α‑Synuclein aggregation, a phenomenon associated with Parkinson disease. In vitro, Hsc70 binds to soluble α‑Syn and slows down its assembly into fibrils. Hsc70 also binds fibrillar α‑Syn, 5-fold tighter than soluble α‑Syn. This interaction reduces the cytotoxicity associated with naked α‑Syn fibrils. Herein, we discuss the feasibility of engineering a "minichaperone" which could be used against α‑Syn assembly propagation in Parkinson disease: taking what is necessary and sufficient within Hsc70 to protect against the damaging repercussions of high molecular weight α‑Syn species' passage from one neuron to another in the brain.

Entities: Disease Gene

Keywords: Hsc70; Parkinson’s disease; alpha synuclein; chaperones; heat shock protein

Year: 2012 PMID： 22482021 PMCID： PMC3291325 DOI： 10.4161/cib.18483

Source DB: PubMed Journal: Commun Integr Biol ISSN： 1942-0889

15 in total

1. Hsc70 protein interaction with soluble and fibrillar alpha-synuclein.

Authors: Samantha Pemberton; Karine Madiona; Laura Pieri; Mehdi Kabani; Luc Bousset; Ronald Melki
Journal: J Biol Chem Date: 2011-08-10 Impact factor: 5.157

Review 2. Heat shock proteins as suppressors of accumulation of toxic prefibrillar intermediates and misfolded proteins in neurodegenerative diseases.

Authors: Shigeki Arawaka; Youhei Machiya; Takeo Kato
Journal: Curr Pharm Biotechnol Date: 2010-02 Impact factor: 2.837

3. The impact of the E46K mutation on the properties of alpha-synuclein in its monomeric and oligomeric states.

Authors: Ross A Fredenburg; Carla Rospigliosi; Robin K Meray; Jeffrey C Kessler; Hilal A Lashuel; David Eliezer; Peter T Lansbury
Journal: Biochemistry Date: 2007-05-26 Impact factor: 3.162

4. Thermodynamic stability and folding of GroEL minichaperones.

Authors: R Golbik; R Zahn; S E Harding; A R Fersht
Journal: J Mol Biol Date: 1998-02-20 Impact factor: 5.469

5. Chaperone activity and structure of monomeric polypeptide binding domains of GroEL.

Authors: R Zahn; A M Buckle; S Perrett; C M Johnson; F J Corrales; R Golbik; A R Fersht
Journal: Proc Natl Acad Sci U S A Date: 1996-12-24 Impact factor: 11.205

6. The diverse members of the mammalian HSP70 machine show distinct chaperone-like activities.

Authors: Jurre Hageman; Maria A W H van Waarde; Alicja Zylicz; Dawid Walerych; Harm H Kampinga
Journal: Biochem J Date: 2011-04-01 Impact factor: 3.857

7. Effect of familial Parkinson's disease point mutations A30P and A53T on the structural properties, aggregation, and fibrillation of human alpha-synuclein.

Authors: J Li; V N Uversky; A L Fink
Journal: Biochemistry Date: 2001-09-25 Impact factor: 3.162

Review 8. Prion-like transmission of protein aggregates in neurodegenerative diseases.

Authors: Patrik Brundin; Ronald Melki; Ron Kopito
Journal: Nat Rev Mol Cell Biol Date: 2010-04 Impact factor: 94.444

9. Differential effects of Hsc70 and Hsp70 on the intracellular trafficking and functional expression of epithelial sodium channels.

Authors: Samuel B Goldfarb; Ossama B Kashlan; Jeffrey N Watkins; Laurence Suaud; Wusheng Yan; Thomas R Kleyman; Ronald C Rubenstein
Journal: Proc Natl Acad Sci U S A Date: 2006-04-03 Impact factor: 11.205

Review 10. Pathogenesis of Parkinson's disease: emerging role of molecular chaperones.

Authors: Rina Bandopadhyay; Jacqueline de Belleroche
Journal: Trends Mol Med Date: 2009-12-24 Impact factor: 11.951

8 in total

1. Low Levels of Prohibitin in Substantia Nigra Makes Dopaminergic Neurons Vulnerable in Parkinson's Disease.

Authors: Debashis Dutta; Nilufar Ali; Emili Banerjee; Raghavendra Singh; Amit Naskar; Ramesh Kumar Paidi; Kochupurackal P Mohanakumar
Journal: Mol Neurobiol Date: 2017-01-06 Impact factor: 5.590

2. Lmx1a and Lmx1b regulate mitochondrial functions and survival of adult midbrain dopaminergic neurons.

Authors: Hélène Doucet-Beaupré; Catherine Gilbert; Marcos Schaan Profes; Audrey Chabrat; Consiglia Pacelli; Nicolas Giguère; Véronique Rioux; Julien Charest; Qiaolin Deng; Ariadna Laguna; Johan Ericson; Thomas Perlmann; Siew-Lan Ang; Francesca Cicchetti; Martin Parent; Louis-Eric Trudeau; Martin Lévesque
Journal: Proc Natl Acad Sci U S A Date: 2016-07-12 Impact factor: 11.205

3. Identification of protein interfaces between α-synuclein, the principal component of Lewy bodies in Parkinson disease, and the molecular chaperones human Hsc70 and the yeast Ssa1p.

Authors: Virginie Redeker; Samantha Pemberton; Willy Bienvenut; Luc Bousset; Ronald Melki
Journal: J Biol Chem Date: 2012-07-26 Impact factor: 5.157