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Allopregnanolone and neuroHIV: Potential benefits of neuroendocrine modulation in the era of antiretroviral therapy.

作者信息

Salahuddin Mohammed F, Qrareya Alaa N, Mahdi Fakhri, Moss Emaya, Akins Nicholas S, Li Jing, Le Hoang V, Paris Jason J

机构信息

Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, USA.

Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, USA.

出版信息

J Neuroendocrinol. 2022 Feb;34(2):e13047. doi: 10.1111/jne.13047. Epub 2021 Oct 14.


DOI:10.1111/jne.13047
PMID:34651359
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8866218/
Abstract

Forty years into the HIV pandemic, approximately 50% of infected individuals still suffer from a constellation of neurological disorders collectively known as 'neuroHIV.' Although combination antiretroviral therapy (cART) has been a tremendous success, in its present form, it cannot eradicate HIV. Reservoirs of virus reside within the central nervous system, serving as sources of HIV virotoxins that damage mitochondria and promote neurotoxicity. Although understudied, there is evidence that HIV or the HIV regulatory protein, trans-activator of transcription (Tat), can dysregulate neurosteroid formation potentially contributing to endocrine dysfunction. People living with HIV commonly suffer from endocrine disorders, including hypercortisolemia accompanied by paradoxical adrenal insufficiency upon stress. Age-related comorbidities often onset sooner and with greater magnitude among people living with HIV and are commonly accompanied by hypogonadism. In the post-cART era, these derangements of the hypothalamic-pituitary-adrenal and -gonadal axes are secondary (i.e., relegated to the brain) and indicative of neuroendocrine dysfunction. We review the clinical and preclinical evidence for neuroendocrine dysfunction in HIV, the capacity for hormone therapeutics to play an ameliorative role and the future steroid-based therapeutics that may have efficacy as novel adjunctives to cART.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/a5a616e8480a/JNE-34-e13047-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/b11193b0d7e2/JNE-34-e13047-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/6aa90b948890/JNE-34-e13047-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/2e1942cb8000/JNE-34-e13047-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/f404dd0a1445/JNE-34-e13047-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/bc8ec7ddbbd5/JNE-34-e13047-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/6c8626bae8cb/JNE-34-e13047-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/a5a616e8480a/JNE-34-e13047-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/b11193b0d7e2/JNE-34-e13047-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/6aa90b948890/JNE-34-e13047-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/2e1942cb8000/JNE-34-e13047-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/f404dd0a1445/JNE-34-e13047-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/bc8ec7ddbbd5/JNE-34-e13047-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/6c8626bae8cb/JNE-34-e13047-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4d2/9135062/a5a616e8480a/JNE-34-e13047-g005.jpg

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Allopregnanolone and neuroHIV: Potential benefits of neuroendocrine modulation in the era of antiretroviral therapy.

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引用本文的文献

[1]
Emotional Disorders, Risk Factors, and Correlations of Post-Partum Depression and Post-Traumatic Stress Disorder with Sexual Function During Post-Partum Period.

Diagnostics (Basel). 2025-4-22

[2]
HIV-1 Tat Impairment of Mitochondrial Respiration via Complexes I and II Can Be Ameliorated by Allopregnanolone in Opioid-Exposed or Opioid-Naïve Cells and Mice.

Antioxidants (Basel). 2025-3-31

[3]
Physiological Corticosterone Attenuates gp120-Mediated Microglial Activation and Is Associated with Reduced Anxiety-Like Behavior in gp120-Expressing Mice.

Viruses. 2023-2-2

本文引用的文献

[1]
Prevention of HIV-1 TAT Protein-Induced Peripheral Neuropathy and Mitochondrial Disruption by the Antimuscarinic Pirenzepine.

Front Neurol. 2021-6-15

[2]
S-Equol mitigates motivational deficits and dysregulation associated with HIV-1.

Sci Rep. 2021-6-4

[3]
HIV-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent with the Potentiation of Oxycodone's Psychomotor Effects in Female Mice.

Viruses. 2021-4-30

[4]
In vivo proton magnetic resonance spectroscopy detection of metabolite abnormalities in aged Tat-transgenic mouse brain.

Geroscience. 2021-8

[5]
HIV-1 Tat and Morphine Differentially Disrupt Pyramidal Cell Structure and Function and Spatial Learning in Hippocampal Area CA1: Continuous versus Interrupted Morphine Exposure.

eNeuro. 2021-5-24

[6]
Neurosteroid allopregnanolone (3α,5α-THP) inhibits inflammatory signals induced by activated MyD88-dependent toll-like receptors.

Transl Psychiatry. 2021-2-26

[7]
Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders.

Cell Mol Life Sci. 2021-5

[8]
Functional Hypogonadism and Testosterone Deficiency in Aging Males With and Without HIV-infection.

Exp Clin Endocrinol Diabetes. 2021-11

[9]
Astrocyte HIV-1 Tat Differentially Modulates Behavior and Brain MMP/TIMP Balance During Short and Prolonged Induction in Transgenic Mice.

Front Neurol. 2020-12-15

[10]
Safety, tolerability, and pharmacokinetics of allopregnanolone as a regenerative therapeutic for Alzheimer's disease: A single and multiple ascending dose phase 1b/2a clinical trial.

Alzheimers Dement (N Y). 2020-12-16

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