Confound, Cause, or Cure: The Effect of Cannabinoids on HIV-Associated Neurological Sequelae

Starr, Alexander; Jordan‐Sciutto, Kelly L.; Mironets, Eugene

doi:10.3390/v13071242

Cited by 4 publications

(2 citation statements)

References 217 publications

(241 reference statements)

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“…Several studies have showed that HIV gp120 stimulates increased cortical fatty acid amide hydrolase (FAAH) [ 47 , 48 ], subsequently allowing for rapid 2-AG and AEA production [ 49 ], selective ligands for the NUCB1 linked to degree of depressive behavior [ 50 ], in the postsynaptic neuron, whereas decreased CNR1 expression promotes the release of 2-AG and AEA [ 51 , 52 ]. Herein, down-regulation of CNR1 expression and up-regulation of NUCB1 expression in neurons were found in the co-occurrence of depression disorder and SHIV infection, as detected by IHC and Western blot.…”

Section: Discussionmentioning

confidence: 99%

Possible Association of Nucleobindin-1 Protein with Depressive Disorder in Patients with HIV Infection

et al. 2022

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Background: Mental disorders linked with dysfunction in the temporal cortex, such as anxiety and depression, can increase the morbidity and mortality of people living with HIV (PLWHA). Expressions of both nucleobindin 1 (NUCB1) and cannabinoid receptor 1 (CNR1) in the neurons have been found to alter in patients with depressive disorder, but whether it is involved in the development of depression in the context of HIV infection is unknown. Objectives To investigate the effects of NUCB1 on depressive disorder among PLWHA and preliminarily explore the underlying molecular mechanisms. Methods: Individuals who were newly HIV diagnosed were assessed on the Hospital Anxiety and Depression scale (HADS). Then SHIV-infected rhesus monkeys were used to investigate the possible involvement of the NUCB1 and the CNR1 protein in depression-like behavior. Results: The prevalence rate of depression among PLWHA was 27.33% (41/150). The mechanism results showing elevated NUCB1 levels in cerebrospinal fluid from HIV-infected patients suffering from depression were confirmed compared to those of HIV-infected patients. Moreover, the immunohistochemical analysis indicated the expression of NUCB1 in the temporal cortex neurons of SHIV-infected monkeys was higher than that of the healthy control. Conversely, CNR1 expression was down-regulated at protein levels. Conclusions: Depression symptoms are common among PLWHA and associate with NUCB1 expression increases, and NUCB1 may be a potential target for depression.

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Section: Discussionmentioning

confidence: 99%

Possible Association of Nucleobindin-1 Protein with Depressive Disorder in Patients with HIV Infection

et al. 2022

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“…Agonists of the CB2R have shown therapeutic potential against HIV-1 replication, neuroinflammation and neurotoxicity in several studies, which have been reviewed by different groups [ 50 , 51 , 52 , 53 , 54 , 55 ], and new supporting evidence continues to emerge [ 14 , 56 ]. In searching for strategies against CATB-induced neurotoxicity, we recently demonstrated that activating the CB2R with agonists decreases HIV-1 replication, CATB secretion, and neurotoxicity from HIV-infected macrophages [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Quantitative Proteomics Reveal That CB2R Agonist JWH-133 Downregulates NF-κB Activation, Oxidative Stress, and Lysosomal Exocytosis from HIV-Infected Macrophages

Rosario-Rodríguez,

Cantres-Rosario,

Carrasquillo-Carrión

et al. 2024

IJMS

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HIV-associated neurocognitive disorders (HAND) affect 15–55% of HIV-positive patients and effective therapies are unavailable. HIV-infected monocyte-derived macrophages (MDM) invade the brain of these individuals, promoting neurotoxicity. We demonstrated an increased expression of cathepsin B (CATB), a lysosomal protease, in monocytes and post-mortem brain tissues of women with HAND. Increased CATB release from HIV-infected MDM leads to neurotoxicity, and their secretion is associated with NF-κB activation, oxidative stress, and lysosomal exocytosis. Cannabinoid receptor 2 (CB2R) agonist, JWH-133, decreases HIV-1 replication, CATB secretion, and neurotoxicity from HIV-infected MDM, but the mechanisms are not entirely understood. We hypothesized that HIV-1 infection upregulates the expression of proteins associated with oxidative stress and that a CB2R agonist could reverse these effects. MDM were isolated from healthy women donors (n = 3), infected with HIV-1ADA, and treated with JWH-133. After 13 days post-infection, cell lysates were labeled by Tandem Mass Tag (TMT) and analyzed by LC/MS/MS quantitative proteomics bioinformatics. While HIV-1 infection upregulated CATB, NF-κB signaling, Nrf2-mediated oxidative stress response, and lysosomal exocytosis, JWH-133 treatment downregulated the expression of the proteins involved in these pathways. Our results suggest that JWH-133 is a potential alternative therapy against HIV-induced neurotoxicity and warrant in vivo studies to test its potential against HAND.

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The Endocannabinoid System as a Potential Therapeutic Target for HIV-1-Associated Neurocognitive Disorder

Chu

Zheng

et al. 2023

Cannabis and Cannabinoid Research

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Confound, Cause, or Cure: The Effect of Cannabinoids on HIV-Associated Neurological Sequelae

Cited by 4 publications

References 217 publications

Possible Association of Nucleobindin-1 Protein with Depressive Disorder in Patients with HIV Infection

Possible Association of Nucleobindin-1 Protein with Depressive Disorder in Patients with HIV Infection

Quantitative Proteomics Reveal That CB2R Agonist JWH-133 Downregulates NF-κB Activation, Oxidative Stress, and Lysosomal Exocytosis from HIV-Infected Macrophages

The Endocannabinoid System as a Potential Therapeutic Target for HIV-1-Associated Neurocognitive Disorder

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