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Intersecting roles of ER stress, mitochondrial dysfunction, autophagy, and calcium homeostasis in HIV-associated neurocognitive disorder

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Abstract

HIV-associated neurocognitive disorder (HAND) is a collective term describing the spectrum of neurocognitive deficits that arise from HIV infection. Although the introduction to highly active antiretroviral therapy (HAART) has prolonged the lifespan of HIV patients, neurocognitive impairments remain prevalent, as patients are left perpetually with HIV. Currently, physicians face a challenge in treating HAND patients, so a greater understanding of the mechanisms underlying HAND pathology has been a growing focus in HIV research. Recent research has revealed the role disrupted calcium homeostasis in HIV-mediated neurotoxicity. Calcium plays a well-established role in the crosstalk between the mitochondrion and ER as well as in regulating autophagy, and ER stress, mitochondrial dysfunction, and impaired autophagic activity are considered hallmarks in several neurodegenerative and neurocognitive disorders. Therefore, it is paramount that the intricate inter-organelle signaling in relation to calcium homeostasis during HIV infection and the development of HAND is elucidated. This review consolidates current knowledge regarding the neuropathology of neurocognitive disorders and HIV infection with a focus on the underlying role of calcium during ER stress, mitochondrial dysfunction, and autophagy associated with the progression of HAND. The details of this intricate crosstalk during HAND remain relatively unknown; further research in this field can potentially aid in the development of improved therapy for patients suffering from HAND.

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Authors and Affiliations

  1. Institute of Human Virology, University of Maryland, 725 W Lombard St, Baltimore, MD, 21201, USA

    Sanketh Andhavarapu, Akhil Katuri, Joseph Bryant, Vivek Patel, Udit Gupta, Girma Asemu & Tapas K. Makar

  2. VA Medical Center, Baltimore, MD, 21201, USA

    Tapas K. Makar

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  1. Sanketh Andhavarapu
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  2. Akhil Katuri
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All authors listed above have significantly contributed to the review and agreed jointly to approve it for publication.

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Andhavarapu, S., Katuri, A., Bryant, J. et al. Intersecting roles of ER stress, mitochondrial dysfunction, autophagy, and calcium homeostasis in HIV-associated neurocognitive disorder. J. Neurovirol. 26, 664–675 (2020). https://doi.org/10.1007/s13365-020-00861-0

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