Excitotoxic programmed cell death involves caspase-independent mechanisms

Research output: Chapter in Book/Report/Conference proceedingChapter


Cell death is a strictly programmed physiological process during the development of living organisms. In conditions like brain trauma, ischemia/reperfusion, brain injury, and cellular stress, cell death becomes unregulated, leading to neurodegenerative processes and stroke. Cell death, in general, is a complex process involving multiple pathways. Apoptosis, necrosis and autophagy are the three traditionally described pathways of cell death. These pathways share many common biochemical events in cell death execution. Apoptosis, in general, is executed by the activation of caspases; and involves the formation of apoptotic bodies without eliciting inflammatory responses. Necrosis, on the other hand, involves massive cell swelling, inflammation and rupture of cellular structures. Autophagy, the third pathway of cell death, was originally identified in the recycling of organelles and proteins. Recent data suggest that autophagy plays a critical role in neurodegenerative processes. Excitotoxicity is a common pathological process in many neurodegenerative disorders, and this process involves over-stimulation of glutamate receptors and an excessive influx of calcium into cells. Cell death in excitotoxicity is unique in that, for the most part, it does not involve caspase-dependent pathways. Overactivation of poly (ADP-ribose) polymerase-1 (PARP-1) is an early pathological event in excitotoxicity that leads to a unique form of cell death called parthanatos. Biochemical events in parthanatos include early accumulation of poly (ADP-ribose) (PAR) and nuclear translocation of apoptosis inducing factor (AIF) from the mitochondria.

Original languageEnglish (US)
Title of host publicationAcute Neuronal Injury
Subtitle of host publicationThe Role of Excitotoxic Programmed Cell Death Mechanisms
PublisherSpringer US
Number of pages10
ISBN (Electronic)9780387732268
ISBN (Print)9780387732251
StatePublished - Jan 1 2010

ASJC Scopus subject areas

  • General Medicine
  • General Neuroscience


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