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Curr Opin Genet Dev. 2017 Jun;44:1-8. doi: 10.1016/j.gde.2017.01.008. Epub 2017 Feb 14.

Designer protein disaggregases to counter neurodegenerative disease.

Author information

1
Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, United States of America. Electronic address: jshorter@mail.med.upenn.edu.

Abstract

Protein misfolding and aggregation unify several devastating neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. There are no effective therapeutics for these disorders and none that target the reversal of the aberrant protein misfolding and aggregation that cause disease. Here, I showcase important advances to define, engineer, and apply protein disaggregases to mitigate deleterious protein misfolding and counter neurodegeneration. I focus on two exogenous protein disaggregases, Hsp104 from yeast and gene 3 protein from bacteriophages, as well as endogenous human protein disaggregases, including: (a) Hsp110, Hsp70, Hsp40, and small heat-shock proteins; (b) HtrA1; and (c) NMNAT2 and Hsp90. I suggest that protein-disaggregase modalities can be channeled to treat numerous fatal and presently incurable neurodegenerative diseases.

PMID:
28208059
PMCID:
PMC5447488
DOI:
10.1016/j.gde.2017.01.008
[Indexed for MEDLINE]
Free PMC Article

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