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Papers

Tat peptides inhibit neprilysin

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Pages 153-160 | Received 13 Jan 2006, Accepted 10 Apr 2006, Published online: 10 Jul 2009
 

Abstract

Dementia associated with human immunodeficiency virus (HIV) infection occurs commonly in the aging population and amyloid depositions are noted in the brains of patients with HIV infection in younger age groups. This suggests a dysregulation of amyloid processing in the setting of HIV infection. The Tat protein of HIV has been implicated in the neuropathogenesis of HIV infection due to its neurotoxic and glial activation properties. However, Tat protein and Tat-derived peptides were recently also shown to inhibit neprilysin, the major amyloid β peptide degrading enzyme in brain, in a cell aggregate system. This effect could contribute to the observed accumulation of amyloid in the brain of HIV-infected patients. The authors report here that peptides derived from the Tat protein, but not Tat protein itself, inhibit homogeneous recombinant neprilysin. This inhibition was found to be competitive and reversible and therefore does not involve covalent bond formation. Tat peptides and Tat protein were slowly hydrolyzed by neprilysin. Thus the accumulation of Tat-derived proteolytic fragments may serve to inhibit neprilysin and increase amyloid β peptide levels. Journal of NeuroVirology (2006) 12, 153–160.

This work was supported in part by grants DA02243 from the National Institute on Drug Abuse, AG024899 from the National Institute on Aging, NS046517 and NS039253 from the National Institute on Neurological Disorders and Stroke, and P20RR02017 from the NCRR.

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