Honokiol hexafluoro confers reversal of neuropathological markers of HIV infection in a murine SCID model

Cognitive impairment remains a persistent challenge in people living with HIV (PWLH) despite antiretroviral therapy (ART) due to ART's inability to eliminate brain HIV. HIV-induced cognitive dysfunction results from immune dysregulation, ongoing neuroinflammation, and the continuous virus prese...

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Published in:Neurotherapeutics 2024-03, Vol.21 (2), p.e00329-e00329, Article e00329
Main Authors: Zhang, Zhan, Scanlan, Aaron, Koneru, Rajeth, Morrell, Chelsea Richardson, Reece, Monica D., Edwards, Emily, Roa, Sebastian, Gavegnano, Christina, Bimonte-Nelson, Heather, Arbiser, Jack, Tyor, William
Format: Article
Language:English
Subjects:
Allyl Compounds
Animals
Biphenyl Compounds
Cognitive dysfunction
HIV
HIV Infections - complications
HIV Infections - drug therapy
HIV Infections - pathology
Honokiol
Humans
Macrophages
Mice
Mice, SCID
Mouse model
Neuroinflammatory Diseases
Phenols
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Summary:Cognitive impairment remains a persistent challenge in people living with HIV (PWLH) despite antiretroviral therapy (ART) due to ART's inability to eliminate brain HIV. HIV-induced cognitive dysfunction results from immune dysregulation, ongoing neuroinflammation, and the continuous virus presence, collectively contributing to cognitive deficits. Therefore, adjunctive therapies are needed to reduce cerebral HIV reservoirs, mitigate neuroinflammation, and impede cognitive dysfunction progression. Our study focused on Honokiol, known for its anti-inflammatory and neuroprotective properties, in an experimental mouse model simulating HIV-induced cognitive dysfunction. Using Honokiol Hexafluoro (HH), a synthetic analogue, we comprehensively evaluated its potential to ameliorate cognitive dysfunction and cerebral pathology in HIV-associated cognitive dysfunction. Our findings showed that HH treatment effectively reversed HIV-induced cognitive dysfunction, concurrently suppressing astrocyte activation, restoring neuronal dendritic arborization, and reducing microglial activation. Furthermore, HH remodeled the metabolic profile of HIV-infected human monocyte-derived macrophages, resulting in decreased activation and the promotion of a quiescent state in vitro.
ISSN:1878-7479
1878-7479
DOI:10.1016/j.neurot.2024.e00329