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. 2012 Jan 1;5(1):94-5.
doi: 10.4161/cib.18483.

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

Samantha Pemberton  1 , Ronald Melki
Affiliations

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

Samantha Pemberton et al. Commun Integr Biol. .

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.

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

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Figures

Figure 1.
Figure 1.
Possible protective mechanism of Hsc70 as a therapeutic agent. A minichaperone based on Hsc70 could be used to reduce the toxicity of α‑Syn fibrils by binding to extracellular fibrils, altering their physicochemical properties, and preventing cell-to-cell propagation.
See this image and copyright information in PMC

Comment on

  • Pemberton S, Madiona K, Pieri L, Kabani M, Bousset L, Melki R. Hsc70 Protein Interaction with Soluble and Fibrillar α‑Synuclein. J Biol Chem. 2011;286:34690–9. doi: 10.1074/jbc.M111.261321.

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