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Nature. 2013 Feb 14;494(7436):201-6. doi: 10.1038/nature11866. Epub 2013 Jan 30.

Identification of a candidate therapeutic autophagy-inducing peptide.

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  • 1Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas 75390, USA.

Abstract

The lysosomal degradation pathway of autophagy has a crucial role in defence against infection, neurodegenerative disorders, cancer and ageing. Accordingly, agents that induce autophagy may have broad therapeutic applications. One approach to developing such agents is to exploit autophagy manipulation strategies used by microbial virulence factors. Here we show that a peptide, Tat-beclin 1-derived from a region of the autophagy protein, beclin 1, which binds human immunodeficiency virus (HIV)-1 Nef-is a potent inducer of autophagy, and interacts with a newly identified negative regulator of autophagy, GAPR-1 (also called GLIPR2). Tat-beclin 1 decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1) in vitro, and reduces mortality in mice infected with chikungunya or West Nile virus. Thus, through the characterization of a domain of beclin 1 that interacts with HIV-1 Nef, we have developed an autophagy-inducing peptide that has potential efficacy in the treatment of human diseases.

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PMID:
23364696
[PubMed - indexed for MEDLINE]
PMCID:
PMC3788641
Free PMC Article

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