Nicotinamide: necessary nutrient emerges as a novel cytoprotectant for the brain.
Although usually identified as an essential cellular nutrient for cellular growth and maintenance, nicotinamide is under development as a novel cytoprotectant for acute and chronic neurodegenerative disorders. Here, we outline support for the premise that nicotinamide both prevents and reverses neuronal and vascular cell injury. Nicotinamide fosters DNA integrity and maintains phosphatidylserine membrane asymmetry to prevent cellular inflammation, cellular phagocytosis and vascular thrombosis. The downstream cellular and molecular cascades are considered vital for the cytoprotection offered by nicotinamide. These pathways encompass the modulation of Akt, the forkhead transcription factor FKHRL1, mitochondrial membrane potential, caspase activities and cellular energy metabolism, but remain independent of intracellular pH and mitogen-activated protein kinases. As both a therapeutic agent and an investigational tool, nicotinamide offers new therapeutic strategies for degenerative disorders of the CNS.
Maiese
Kenneth
K
Division of Cellular and Molecular Cerebral Ischemia, Wayne State University, School of Medicine Detroit, St Antoine, MI 48201, USA. kmaiese@med.wayne.edu
Chong
Zhao Zhong
ZZ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009536:Niacinamide / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D009536:Niacinamide