Druggable targets of the endocannabinoid system: Implications for the treatment of HIV-associated neurocognitive disorder

Mariah M. Wu; Xinwen Zhang; Melissa J Asher; Stanley A. Thayer

doi:10.1016/j.brainres.2019.146467

Druggable targets of the endocannabinoid system: Implications for the treatment of HIV-associated neurocognitive disorder

Mariah M. Wu, Xinwen Zhang, Melissa J Asher, Stanley A. Thayer

Research output: Contribution to journal › Review article › peer-review

12 Scopus citations

Abstract

HIV-associated neurocognitive disorder (HAND) affects nearly half of all HIV-infected individuals. Synaptodendritic damage correlates with neurocognitive decline in HAND, and many studies have demonstrated that HIV-induced neuronal injury results from excitotoxic and inflammatory mechanisms. The endocannabinoid (eCB) system provides on-demand protection against excitotoxicity and neuroinflammation. Here, we discuss evidence of the neuroprotective and anti-inflammatory properties of the eCB system from in vitro and in vivo studies. We examine the pharmacology of the eCB system and evaluate the therapeutic potential of drugs that modulate eCB signaling to treat HAND. Finally, we provide perspective on the need for additional studies to clarify the role of the eCB system in HIV neurotoxicity and speculate that strategies that enhance eCB signaling might slow cognitive decline in HAND.

Original language	English (US)
Article number	146467
Journal	Brain Research
Volume	1724
DOIs	https://doi.org/10.1016/j.brainres.2019.146467
State	Published - Dec 1 2019

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grants DA007304 and DA044809 to ST. MW was supported by NIH training grant T32 DA007097.

Publisher Copyright:
© 2019 Elsevier B.V.

Keywords

2-Arachidonoylglycerol
Anandamide
Cannabinoid receptor
Fatty acid amide hydrolase
HIV-1
Monoacylglycerol lipase

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Druggable targets of the endocannabinoid system: Implications for the treatment of HIV-associated neurocognitive disorder",

abstract = "HIV-associated neurocognitive disorder (HAND) affects nearly half of all HIV-infected individuals. Synaptodendritic damage correlates with neurocognitive decline in HAND, and many studies have demonstrated that HIV-induced neuronal injury results from excitotoxic and inflammatory mechanisms. The endocannabinoid (eCB) system provides on-demand protection against excitotoxicity and neuroinflammation. Here, we discuss evidence of the neuroprotective and anti-inflammatory properties of the eCB system from in vitro and in vivo studies. We examine the pharmacology of the eCB system and evaluate the therapeutic potential of drugs that modulate eCB signaling to treat HAND. Finally, we provide perspective on the need for additional studies to clarify the role of the eCB system in HIV neurotoxicity and speculate that strategies that enhance eCB signaling might slow cognitive decline in HAND.",

keywords = "2-Arachidonoylglycerol, Anandamide, Cannabinoid receptor, Fatty acid amide hydrolase, HIV-1, Monoacylglycerol lipase",

author = "Wu, {Mariah M.} and Xinwen Zhang and Asher, {Melissa J} and Thayer, {Stanley A.}",

note = "Funding Information: This work was supported by National Institutes of Health Grants DA007304 and DA044809 to ST. MW was supported by NIH training grant T32 DA007097. Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",

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AU - Wu, Mariah M.

AU - Zhang, Xinwen

AU - Asher, Melissa J

AU - Thayer, Stanley A.

N1 - Funding Information: This work was supported by National Institutes of Health Grants DA007304 and DA044809 to ST. MW was supported by NIH training grant T32 DA007097. Publisher Copyright: © 2019 Elsevier B.V.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - HIV-associated neurocognitive disorder (HAND) affects nearly half of all HIV-infected individuals. Synaptodendritic damage correlates with neurocognitive decline in HAND, and many studies have demonstrated that HIV-induced neuronal injury results from excitotoxic and inflammatory mechanisms. The endocannabinoid (eCB) system provides on-demand protection against excitotoxicity and neuroinflammation. Here, we discuss evidence of the neuroprotective and anti-inflammatory properties of the eCB system from in vitro and in vivo studies. We examine the pharmacology of the eCB system and evaluate the therapeutic potential of drugs that modulate eCB signaling to treat HAND. Finally, we provide perspective on the need for additional studies to clarify the role of the eCB system in HIV neurotoxicity and speculate that strategies that enhance eCB signaling might slow cognitive decline in HAND.

AB - HIV-associated neurocognitive disorder (HAND) affects nearly half of all HIV-infected individuals. Synaptodendritic damage correlates with neurocognitive decline in HAND, and many studies have demonstrated that HIV-induced neuronal injury results from excitotoxic and inflammatory mechanisms. The endocannabinoid (eCB) system provides on-demand protection against excitotoxicity and neuroinflammation. Here, we discuss evidence of the neuroprotective and anti-inflammatory properties of the eCB system from in vitro and in vivo studies. We examine the pharmacology of the eCB system and evaluate the therapeutic potential of drugs that modulate eCB signaling to treat HAND. Finally, we provide perspective on the need for additional studies to clarify the role of the eCB system in HIV neurotoxicity and speculate that strategies that enhance eCB signaling might slow cognitive decline in HAND.

KW - 2-Arachidonoylglycerol

KW - Anandamide

KW - Cannabinoid receptor

KW - Fatty acid amide hydrolase

KW - HIV-1

KW - Monoacylglycerol lipase

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Druggable targets of the endocannabinoid system: Implications for the treatment of HIV-associated neurocognitive disorder

Abstract

Bibliographical note

Keywords

UN SDGs

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