Excitotoxicity: Bridge to various triggers in neurodegenerative disorders

Glutamate is one of the most prominent neurotransmitter in the body, present in over 50% of nervous tissue and plays an important role in neuronal excitation. This neuronal excitation is short-lived and is followed by depression. Multiple abnormal triggers such as energy deficiency, oxidative stress, mitochondrial dysfunction, calcium overload, etc can lead to aberration in neuronal excitation process. Such an aberration, serves as a common pool or bridge between abnormal triggers and deleterious signaling processes with which central neurons cannot cope up, leading to death. Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. Such excitotoxic neuronal death has been implicated in spinal cord injury, stroke, traumatic brain injury, hearing loss and in neurodegenerative diseases of the central nervous system such as stroke, epilepsy, multiple sclerosis, Alzheimer disease, Amyltropic lateral sclerosis, Parkinson's disease, Huntington disease and alcohol withdrawal. This review mainly emphasizes the triggering events which sustain neuronal excitation, role of calcium, mitochondrial dysfunction, ROS, NO, chloride homeostasis and eicosanoids pathways. Further, a brief introduction about the recent research occurring in the treatment of various neurodegenerative diseases, including a summary of the presumed physiologic mechanisms behind the pharmacology of these disorders. (C) 2012 Elsevier B.V. All rights reserved.