Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6020179 | Journal of Neuroimmunology | 2015 | 13 Pages |
â¢HIV-1 differentially modulates neuro-glial toxicity.â¢HIV-1 induces neuro-glial damage by suppressing autophagy.â¢Suppression of autophagy in neuro-glial cells by HIV-1 is without viral infection.â¢Autophagy induction in neuro-glial cells protects against HIV-1 insult.
Autophagy, a lysosomal degradative pathway that maintains cellular homeostasis, has emerged as an innate immune defense against pathogens. The role of autophagy in the deregulated HIV-infected central nervous system (CNS) is unclear. We have found that HIV-1-induced neuro-glial (neurons and astrocytes) damage involves modulation of the autophagy pathway. Neuro-glial stress induced by HIV-1 led to biochemical and morphological dysfunctions. X4 HIV-1 produced neuro-glial toxicity coupled with suppression of autophagy, while R5 HIV-1-induced toxicity was restricted to neurons. Rapamycin, a specific mTOR inhibitor (autophagy inducer) relieved the blockage of the autophagy pathway caused by HIV-1 and resulted in neuro-glial protection. Further understanding of the regulation of autophagy by cytokines and chemokines or other signaling events may lead to recognition of therapeutic targets for neurodegenerative diseases.