Abstract
It has been well documented that methamphetamine induces microglial activation and death, however, the molecular mechanisms underlying this process remain poorly understood. In the present study, we demonstrated the involvement of sigma-1 receptor (σ-1R) in methamphetamine-mediated microglial apoptosis. Exposure of BV-2 cells to methamphetamine induces cell apoptosis through its cognate receptor σ-1R, followed by activation of the mitogen-activated protein kinases, phosphatidylinositol-3' kinase/Akt as well as the downstream transcription factor p53 pathways. Blockage of σ -1R significantly inhibited the increased pro-apoptotic proteins such as Bax, Caspase-3 and Caspase-9 induced by methamphetamine. In conclusion, these findings underscore the critical role of σ-1R in microglial apoptosis induced by methamphetamine. Understanding the link between σ -1R and apoptosis will lead to development of therapeutic strategies targeting methamphetamine-mediated microglial death/dysfunction.
Keywords: Apoptosis, σ-1R, methamphetamine, microglia.
CNS & Neurological Disorders - Drug Targets
Title:Molecular Mechanisms Involving Sigma-1 Receptor in Cell Apoptosis of BV-2 Microglial Cells Induced by Methamphetamine
Volume: 15 Issue: 7
Author(s): Kai Shen, Yuan Zhang, Xuan Lv, Xufeng Chen, Rongbin Zhou, Lan K. Nguyen, Xiaodong Wu and Honghong Yao
Affiliation:
Keywords: Apoptosis, σ-1R, methamphetamine, microglia.
Abstract: It has been well documented that methamphetamine induces microglial activation and death, however, the molecular mechanisms underlying this process remain poorly understood. In the present study, we demonstrated the involvement of sigma-1 receptor (σ-1R) in methamphetamine-mediated microglial apoptosis. Exposure of BV-2 cells to methamphetamine induces cell apoptosis through its cognate receptor σ-1R, followed by activation of the mitogen-activated protein kinases, phosphatidylinositol-3' kinase/Akt as well as the downstream transcription factor p53 pathways. Blockage of σ -1R significantly inhibited the increased pro-apoptotic proteins such as Bax, Caspase-3 and Caspase-9 induced by methamphetamine. In conclusion, these findings underscore the critical role of σ-1R in microglial apoptosis induced by methamphetamine. Understanding the link between σ -1R and apoptosis will lead to development of therapeutic strategies targeting methamphetamine-mediated microglial death/dysfunction.
Export Options
About this article
Cite this article as:
Shen Kai, Zhang Yuan, Lv Xuan, Chen Xufeng, Zhou Rongbin, Nguyen K. Lan, Wu Xiaodong and Yao Honghong, Molecular Mechanisms Involving Sigma-1 Receptor in Cell Apoptosis of BV-2 Microglial Cells Induced by Methamphetamine, CNS & Neurological Disorders - Drug Targets 2016; 15 (7) . https://dx.doi.org/10.2174/1871527315666160518122816
DOI https://dx.doi.org/10.2174/1871527315666160518122816 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
5'-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications
Current Medicinal Chemistry Aldose Reductase in Diabetic Microvascular Complications
Current Drug Targets HIV-1-Associated Dementia During HAART Therapy
Recent Patents on CNS Drug Discovery (Discontinued) Nasal Polyposis: An Overview of Differential Diagnosis and Treatment
Recent Patents on Inflammation & Allergy Drug Discovery The Role of Disproportionality Analysis of Pharmacovigilance Databases in Safety Regulatory Actions: a Systematic Review
Current Drug Safety Organotypic Hippocampal Slice Cultures for Studies of Brain Damage, Neuroprotection and Neurorepair
Current Drug Targets - CNS & Neurological Disorders Atheroprotective Properties of Pigment Epithelium-Derived Factor (PEDF) in Cardiometabolic Disorders
Current Pharmaceutical Design Editorial (Thematic Issue: New Horizon in the Treatment of Hypertension - Role for Ca Channel Blockers - Why do Ca Channel Blockers be Focused on?)
Current Hypertension Reviews The Effect of the Antioxidant Drug "U-74389G" on Oophoritis During Ischemia Reperfusion Injury in Rats
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Is VEGF a Key Target of Cotinine and Other Potential Therapies Against Alzheimer Disease?
Current Alzheimer Research Commentary (Research Highlights: Targeted Inhibition of miR-155 Promotes Post-Stroke Neovascularization and Functional Recovery)
CNS & Neurological Disorders - Drug Targets Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies
Current Gene Therapy Development of Novel Therapeutics Targeting Isocitrate Dehydrogenase Mutations in Cancer
Current Topics in Medicinal Chemistry Psychotic (Delusional) Major Depression in the Elderly: A Review
Current Psychiatry Reviews Astrocytic Target Mechanisms in Epilepsy
Current Medicinal Chemistry Meet Our Editorial Board Member
Current Medical Imaging Dendritic Cells and their Receptors in Antitumor Immune Response
Current Molecular Medicine Recombinant Antibody Fragments for Neurodegenerative Diseases
Current Neuropharmacology Sphingolipids as Emerging Drug Targets: Therapeutic Applications of Ceramide Analogs
Drug Design Reviews - Online (Discontinued) Understanding The Role of Inflammasome in Angina Pectoris
Current Protein & Peptide Science