A potentially critical role of phospholipases in central nervous system ischemic, traumatic, and neurodegenerative disorders
- 作者：Phillis ; John W. ; O'Regan ; Michael H.
- 关键词：Disorders of the Nervous System ; Ischemia ; Trauma ; Central nervous system ; Free fatty acids ; Phospholipase A ; Phospholipase C ; Phospholipase D ; Arachidonic acid ; Docosahexaenoic acid ; Stroke ; Trauma ; Neurodegeneration
- 刊名：Brain Research Reviews
- 出版年：2004
- 期刊代码：11_01650173
- 类别：neu
- 出版时间：January, 2004
- 卷：44
- 期：1
- 页码：13-47
- 文件大小：762 K
摘要
Phospholipases are a diverse group of enzymes whose activation may be responsible for the development of injury following insult to the brain. Amongst the numerous isoforms of phospholipase proteins expressed in mammals are 19 different phospholipase A2's (PLA2s), classified functionally as either secretory, calcium dependent, or calcium independent, 11 isozymes belonging to three structural groups of PLC, and 3 PLD gene products. Many of these phospholipases have been identified in selected brain regions. Under normal conditions, these enzymes regulate the turnover of free fatty acids (FFAs) in membrane phospholipids affecting membrane stability, fluidity, and transport processes. The measurement of free fatty acids thus provides a convenient method to follow phospholipase activity and their regulation. Phospholipase activity is also responsible for the generation of an extensive list of intracellular messengers including arachidonic acid metabolites. Phospholipases are regulated by many factors including selective phosphorylation, intracellular calcium and pH. However, under abnormal conditions, excessive phospholipase activation, along with a decreased ability to resynthesize membrane phospholipids, can lead to the generation of free radicals, excitotoxicity, mitochondrial dysfunction, and apoptosis/necrosis. This review evaluates the critical contribution of the various phospholipases to brain injury following ischemia and trauma and in neurodegenerative diseases.