title: Anti-apoptotic and anti-oxidative mechanisms of minocycline against sphingomyelinase/ceramide neurotoxicity: implication in Alzheimer's disease and cerebral ischemia.
abstract: Sphingolipids represent a major class of lipids in which selected family members act as bioactive molecules that control diverse cellular processes, such as proliferation, differentiation, growth, senescence, migration and apoptosis. Emerging evidence reveals that sphingomyelinase/ceramide pathway plays a pivotal role in neurodegenerative diseases that involve mitochondrial dysfunction, oxidative stress and apoptosis. Minocycline, a semi-synthetic second-generation tetracycline derivative in clinical use for infection control, is also considered an effective protective agent in various neurodegenerative diseases in pre-clinical studies. Acting via multiple mechanisms, including anti-inflammatory, anti-oxidative and anti-apoptotic effects, minocycline is a desirable candidate for clinical trials in both acute brain injury as well as chronic neurodegenerative disorders. This review is focused on the anti-apoptotic and anti-oxidative mechanisms of minocycline against neurotoxicity induced by sphingomyelinase/ceramide in relation to neurodegeneration, particularly Alzheimer's disease and cerebral ischemia.
authors.affiliation: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Shang-Der
authors.initials: SD
authors.lastname: Chen
authors.forename: Jiu-Haw
authors.initials: JH
authors.lastname: Yin
authors.forename: Chi-Shin
authors.initials: CS
authors.lastname: Hwang
authors.forename: Ching-Min
authors.initials: CM
authors.lastname: Tang
authors.forename: Ding-I
authors.initials: DI
authors.lastname: Yang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002518:Ceramides; D019253:Proto-Oncogene Proteins c-bcl-2; D009569:Nitric Oxide; D013879:Thioredoxins; D013108:Sphingomyelin Phosphodiesterase; D008911:Minocycline; D006152:Cyclic GMP