NDLI: CB2 Receptor Agonists Protect Human Dopaminergic Neurons against Damage from HIV-1 gp120

Content Provider	PubMed Central
Author	Hu, Shuxian Sheng, Wen S. Rock, R. Bryan
Editor	Schindler, Michael
Copyright Year	2013
Abstract	Despite the therapeutic impact of anti-retroviral therapy, HIV-1-associated neurocognitive disorder (HAND) remains a serious threat to AIDS patients, and there currently remains no specific therapy for the neurological manifestations of HIV-1. Recent work suggests that the nigrostriatal dopaminergic area is a critical brain region for the neuronal dysfunction and death seen in HAND and that human dopaminergic neurons have a particular sensitivity to gp120-induced damage, manifested as reduced function (decreased dopamine uptake), morphological changes, and reduced viability. Synthetic cannabinoids inhibit HIV-1 expression in human microglia, suppress production of inflammatory mediators in human astrocytes, and there is substantial literature demonstrating the neuroprotective properties of cannabinoids in other neuropathogenic processes. Based on these data, experiments were designed to test the hypothesis that synthetic cannabinoids will protect dopaminergic neurons against the toxic effects of the HIV-1 protein gp120. Using a human mesencephalic neuronal/glial culture model, which contains dopaminergic neurons, microglia, and astrocytes, we were able to show that the CB1/CB2 agonist WIN55,212-2 blunts gp120-induced neuronal damage as measured by dopamine transporter function, apoptosis and lipid peroxidation; these actions were mediated principally by the CB2 receptor. Adding supplementary human microglia to our cultures enhances gp120-induced damage; WIN55,212-2 is able to alleviate this enhanced damage. Additionally, WIN55,212-2 inhibits gp120-induced superoxide production by purified human microglial cells, inhibits migration of human microglia towards supernatants generated from gp120-stimulated human mesencephalic neuronal/glial cultures and reduces chemokine and cytokine production from the human mesencephalic neuronal/glial cultures. These data suggest that synthetic cannabinoids are capable of protecting human dopaminergic neurons from gp120 in a variety of ways, acting principally through the CB2 receptors and microglia.
Related Links	http://dx.doi.org/10.1371/journal.pone.0077577
Starting Page	77577
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	10
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-10-17
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease

Protection against HIV-1 gp120-induced brain damage by neuronal expression of human amyloid precursor protein

Antioxidants protect PINK1-dependent dopaminergic neurons in Drosophila

HIV-1 gp120 Promotes Lysosomal Exocytosis in Human Schwann Cells

Neutralization of multiple laboratory and clinical isolates of human immunodeficiency virus type 1 (HIV-1) by antisera raised against gp120 from the MN isolate of HIV-1.

Preferential sensitivity of human dopaminergic neurons to gp120-induced oxidative damage

Curcumin Protects Microglia and Primary Rat Cortical Neurons against HIV-1 gp120-Mediated Inflammation and Apoptosis

Antioxidant enzyme gene delivery to protect from HIV-1 gp120-induced neuronal apoptosis

FDA-Approved Drugs that Protect Mammalian Neurons from Glucose Toxicity Slow Aging Dependent on Cbp and Protect Against Proteotoxicity

CB2 Receptor Agonists Protect Human Dopaminergic Neurons against Damage from HIV-1 gp120

Similar Documents

Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: relevance for Huntington’s disease

Protection against HIV-1 gp120-induced brain damage by neuronal expression of human amyloid precursor protein

Antioxidants protect PINK1-dependent dopaminergic neurons in Drosophila

HIV-1 gp120 Promotes Lysosomal Exocytosis in Human Schwann Cells

Neutralization of multiple laboratory and clinical isolates of human immunodeficiency virus type 1 (HIV-1) by antisera raised against gp120 from the MN isolate of HIV-1.

Preferential sensitivity of human dopaminergic neurons to gp120-induced oxidative damage

Curcumin Protects Microglia and Primary Rat Cortical Neurons against HIV-1 gp120-Mediated Inflammation and Apoptosis

Antioxidant enzyme gene delivery to protect from HIV-1 gp120-induced neuronal apoptosis

FDA-Approved Drugs that Protect Mammalian Neurons from Glucose Toxicity Slow Aging Dependent on Cbp and Protect Against Proteotoxicity

CB2 Receptor Agonists Protect Human Dopaminergic Neurons against Damage from HIV-1 gp120