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Role of Neurotrophic Factor Alterations in the Neurodegenerative Process in HIV Associated Neurocognitive Disorders

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Abstract

Migration of HIV infected cells into the CNS is associated with a spectrum of neurological disorders, ranging from milder forms of HIV-associated neurocognitive disorders (HAND) to HIV-associated dementia (HAD). These neuro-psychiatric syndromes are related to the neurodegenerative pathology triggered by the release of HIV proteins and cytokine/chemokines from monocytes/macrophages into the CNS –a condition known as HIV encephalitis (HIVE). As a result of more effective combined anti-retroviral therapy patients with HIV are living longer and thus the frequency of HAND has increased considerably, resulting in an overlap between the neurodegenerative pathology associated with HIV and that related to aging. In fact, HIV infection is believed to hasten the aging process. The mechanisms through which HIV and aging lead to neurodegeneration include: abnormal calcium flux, excitotoxicity, signaling abnormalities, oxidative stress and autophagy defects. Moreover, recent studies have shown that defects in the processing and transport of neurotrophic factors such as fibroblast growth factors (FGFs), neural growth factor (NGF) and brain-derived growth factor (BDNF) might also play a role. Recent evidence implicates alterations in neurotrophins in the pathogenesis of neurodegeneration associated with HAND in the context of aging. Here, we report FGF overexpression curtails gp120-induced neurotoxicity in a double transgenic mouse model. Furthermore, our data show disparities in brain neurotrophic factor levels may be exacerbated in HIV patients over 50 years of age. In this review, we discuss the most recent findings on neurotrophins and HAND in the context of developing new therapies to combat HIV infection in the aging population.

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The funding source had no role in the study design, data collection, data analysis, data interpretation or writing of this report. The corresponding author had full access to all the data and had final responsibility for the decision to submit the paper for publication.

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  1. Department of Pathology, University of California San Diego, La Jolla, CA, USA

    Jerel Fields, Wilmar Dumaop & E. Masliah

  2. Department of Neurosciences, School of Medicine, University of California San Diego, 9500 Gilman Dr., MTF 348, La Jolla, CA, 92093-0624, USA

    Edward Rockenstein & E. Masliah

  3. Department of Neuroscience, Temple University School of Medicine, Philadelphia, PA, USA

    T. D. Langford

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  1. Jerel Fields
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Correspondence to E. Masliah.

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Fields, J., Dumaop, W., Langford, T.D. et al. Role of Neurotrophic Factor Alterations in the Neurodegenerative Process in HIV Associated Neurocognitive Disorders. J Neuroimmune Pharmacol 9, 102–116 (2014). https://doi.org/10.1007/s11481-013-9520-2

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