in Stroke and Neurodegenerative Diseases

Copyright © 2015 Howard Prentice et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In stroke and neurodegenerative disease, neuronal excitotoxicity, caused by increased extracellular glutamate levels, is known to result in calcium overload and mitochondrial dysfunction. Mitochondrial deficits may involve a deficiency in energy supply as well as generation of high levels of oxidants which are key contributors to neuronal cell death through necrotic and apoptotic mechanisms. Excessive glutamate receptor stimulation also results in increased nitric oxide generation which can be detrimental to cells as nitric oxide interacts with superoxide to form the toxic molecule peroxynitrite. High level oxidant production elicits neuronal apoptosis through the actions of proapoptotic Bcl-2 family members resulting in mitochondrial permeability transition pore opening. In addition to apoptotic responses to severe stress, accumulation of misfolded proteins and high levels of oxidants can elicit endoplasmic reticulum (ER) stress pathways which may also contribute to induction of apoptosis. Two categories of therapeutics are discussed that impact major pro-death events that include induction of oxidants, calcium overload, and ER stress. The first category of therapeutic agent includes the amino acid taurine which prevents calcium overload and is also capable of preventing ER stress by inhibiting specific ER stress pathways. The second category involves N-methyl-D-aspartat