Neuroinflammation & pre-mature aging in the context of chronic HIV infection and drug abuse: Role of dysregulated autophagy

Ming Lei Guo, Shilpa Buch

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

In the era of combined antiretroviral therapy (cART), HIV-1 infection has transformed from a death sentence to a manageable, chronic disease. Although the life expectancy of HIV+ individuals is comparable to that of the uninfected subjects paradoxically, there is increased prevalence of age-associated comorbidities such as atherosclerosis, diabetes, osteoporosis & neurological deficits in the context of HIV infection. Drug abuse is a common comorbidity of HIV infection and is often associated with increased neurological complications. Chronic neuroinflammation (abnormal microglial and astrocyte activation) and neuronal synaptodendritic injury are the features of CNS pathology observed in HIV (+) individuals that are taking cART & that abuse drugs. Neuroinflammation is the driving force underlying premature aging associated with HIV (+) infection, cART and drugs of abuse. Autophagy is a highly conserved process critical for maintaining cellular homeostasis. Dysregulated autophagy has been shown to be linked with abnormal immune responses & aging. Recent emerging evidence implicates the role of HIV/HIV proteins, cART, & abused drugs in disrupting the autophagy process in brain cells such as microglia, astrocytes, and neurons. It can thus be envisioned that co-exposure of CNS cells to HIV proteins, cART and/or abused drugs could have synergistic effects on the autophagy process, thereby leading to exaggerated microglial/astrocyte activation, ultimately, promoting the aging process. Restoration of autophagic function could thus provide an alternative therapeutic strategy for mitigating neuroinflammation & ameliorating the premature aging process. The current review aims to unravel the role of dysregulated autophagy in the context of single or co-exposure of microglia, astrocytes, and neurons to HIV/HIV proteins, drugs of abuse &/or cART and will also discuss the pathways involved in dysregulated autophagy-mediated neuroinflammation.

Original languageEnglish (US)
Article number146446
JournalBrain Research
Volume1724
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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