alexa The Impact of HAART on Advanced Brain Aging: Implications for Mitochondrial Dysfunction and APP Processing
ISSN: 1948-5964

Journal of Antivirals & Antiretrovirals
Open Access

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Review Article

The Impact of HAART on Advanced Brain Aging: Implications for Mitochondrial Dysfunction and APP Processing

Julia Campos de O’ Leary1 , Demian Obregon1,2,3, Frank Fernandez1,2, Jun Tan1,2,3 and Brian Giunta1,3*

1Neuroimmunology Laboratory, Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

2Rashid Laboratory for Developmental Neurobiology, Department of Psychiatry and Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

3James A. Haley Veterans’ Administration Hospital, Tampa, FL, USA

*Corresponding Author:
Brian Giunta M.D., Ph.D
Neuroimmunology Laboratory
Department of Psychiatry and Behavioral Neurosciences
Morsani College of Medicine
University of South Florida, Tampa, FL, USA
E-mail: [email protected]

Received Date: April 03, 2012; Accepted Date: May 14, 2012; Published Date: May 16, 2012

Citation: de O’ Leary JC, Obregon D, Fernandez F, Tan J, Giunta B (2012) The Impact of HAART on Advanced Brain Aging: Implications for Mitochondrial Dysfunction and APP Processing. J Antivir Antiretrovir S10. doi: 10.4172/jaa.S10-003

Copyright: © 2012 de O’ Leary JC, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Highly Active Antiretroviral Therapy (HAART) has significantly reduced AIDS-related morbidity and mortality. However the prevalence of HIV-1-Associated Neurocognitive Disorders (HAND) has been on the rise in the post- HAART era. A majority of the side effects of HAART can in part at least be attributed directly, or indirectly, to mitochondrial dysfunction. Indeed the rapid early clinical phase-in of HAART required dose de-escalations secondary to toxicities suggested to be related to drug side effects affecting mitochondria. Central to central nervous system (CNS) function is the amyloid precursor protein (APP), the parent protein from which amyloid-beta (Aβ) peptide is generated. Aβ generation and aggregation as plaques are well known in the age related dementia, Alzheimer’s disease (AD). It has been demonstrated that Aβ is common feature of the HIV infected brain as well. Further, reactive oxygen species (ROS) production is upregulated by HAART. Importantly, ROS promote β-secretase expression; a mechanism by which HAART may promote cognitive dysfunction, even in immune-competent HIV infected individuals.

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