title: Multiple interacting cell death mechanisms in the mediation of excitotoxicity and ischemic brain damage: a challenge for neuroprotection.
abstract: There is currently no approved neuroprotective pharmacotherapy for acute conditions such as stroke and cerebral asphyxia. One of the reasons for this may be the multiplicity of cell death mechanisms, because inhibition of a particular mechanism leaves the brain vulnerable to alternative ones. It is therefore essential to understand the different cell death mechanisms and their interactions. We here review the multiple signaling pathways underlying each of the three main morphological types of cell death--apoptosis, autophagic cell death and necrosis--emphasizing their importance in the neuronal death that occurs during cerebral ischemia and hypoxia-ischemia, and we analyze the interactions between the different mechanisms. Finally, we discuss the implications of the multiplicity of cell death mechanisms for the design of neuroprotective strategies.
authors.affiliation: Département des Neurosciences Fondamentales, Université de Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland. JulienPierre.Puyal@unil.ch
authors.forename: Julien
authors.initials: J
authors.lastname: Puyal
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ginet
authors.forename: Peter G H
authors.initials: PG
authors.lastname: Clarke
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D006801:Humans; D009336:Necrosis / Q000188:drug therapy / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents