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Yin and Yang of PDGF-mediated Signaling Pathway in the Context of HIV Infection and Drug Abuse

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Abstract

The control and eradication of neurological complications associated with AIDS continues to be an important goal in efforts toward improving the well being of HIV-infected patients. Although combined antiretroviral therapies have contributed significantly to increasing the longevity of patients by suppressing the virus burden in the systemic compartments, the prevalence of HIV-associated neurological disorders continues to be on the rise. This in turn, leads to an impaired quality of life of the infected individuals who continue to suffer from mild to moderate cognitive decline and memory loss. Developing therapeutic interventions that reverse neuronal injury in the context of HIV infection, is thus of paramount importance in the field. Our previous studies have demonstrated that platelet-derived growth factor (PDGF) has a neuroprotective potential against HIV envelope protein gp120 and Tat. Paradoxically, PDGF is also a cerebrovascular permeant with deleterious effects on the blood–brain barrier resulting in increased influx of monocytes in the CNS. Herein, we review the opposing roles of PDGF in the context of HIV-associated neurodegenerative disorder (HAND).

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Abbreviations

BDNF:

brain-derived neurotrophic factor

cART:

combination antiretroviral therapy

FGF:

fibroblast growth factor

GDNF:

glia cell line-derived neurotrophic factor

GSK3β:

glycogen synthase kinase-3β

HAND:

HIV-associated neurodegenerative disorder

LTP:

long-term potentiation

MCP-1:

monocyte chemotactic protein-1

NGF:

nerve growth factor

NICD:

Notch intracellular domain

NPC:

neural stem/progenitor cells

PDGF:

platelet derived growth factor

PI-3K:

phosphatidylinositol-3 kinase

TH:

tyrosine hydroxylase

TRPC:

transient receptor potential canonical

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Acknowledgement

This work was supported by grants DA020392, DA033150,DA024442, DA035203, DA033614 (SB) and DA030285 (HY) from the National Institutes of Health.

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  1. Department of Pharmacology and Experimental Neuroscience, 985880 Nebraska Medical Center (DRC 8011), University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA

    Honghong Yao, Crystal Bethel-Brown, Fang Niu, Lu Yang, Fuwang Peng & Shilpa Buch

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  1. Honghong Yao
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  2. Crystal Bethel-Brown
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  3. Fang Niu
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  4. Lu Yang
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  5. Fuwang Peng
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Correspondence to Shilpa Buch.

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Yao, H., Bethel-Brown, C., Niu, F. et al. Yin and Yang of PDGF-mediated Signaling Pathway in the Context of HIV Infection and Drug Abuse. J Neuroimmune Pharmacol 9, 161–167 (2014). https://doi.org/10.1007/s11481-013-9481-5

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