Role of Autophagy in HIV-1 and Drug Abuse-Mediated Neuroinflammaging

Susmita Sil, Annadurai Thangaraj, Abiola Oladapo, Guoku Hu, Naseer A. Kutchy, Ke Liao, Shilpa Buch, Palsamy Periyasamy

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

Chronic low-grade inflammation remains an essential feature of HIV-1 infection under combined antiretroviral therapy (cART) and contributes to the accelerated cognitive defects and aging in HIV-1 infected populations, indicating cART limitations in suppressing viremia. Interestingly, ~50% of the HIV-1 infected population on cART that develops cognitive defects is complicated by drug abuse, involving the activation of cells in the central nervous system (CNS) and neurotoxin release, altogether leading to neuroinflammation. Neuroinflammation is the hallmark feature of many neurodegenerative disorders, including HIV-1-associated neurocognitive disorders (HAND). Impaired autophagy has been identified as one of the underlying mechanisms of HAND in treated HIV-1-infected people that also abuse drugs. Several lines of evidence suggest that autophagy regulates CNS cells' responses and maintains cellular hemostasis. The impairment of autophagy is associated with low-grade chronic inflammation and immune senescence, a known characteristic of pathological aging. Therefore, autophagy impairment due to CNS cells, such as neurons, microglia, astrocytes, and pericytes exposure to HIV-1/HIV-1 proteins, cART, and drug abuse could have combined toxicity, resulting in increased neuroinflammation, which ultimately leads to accelerated aging, referred to as neuroinflammaging. In this review, we focus on the potential role of autophagy in the mechanism of neuroinflammaging in the context of HIV-1 and drug abuse.

Original languageEnglish (US)
Article number44
JournalViruses
Volume15
Issue number1
DOIs
StatePublished - Dec 23 2022

Keywords

  • HIV-1
  • aging
  • autophagy
  • drug abuse
  • neuroinflammation

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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