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- Vol.41 No.12
- CLINICA NEUROL, 41: 1067－1069, 2001
- Vol.41 No.12 contents
The 42nd Annual Meeting of the Japanese Society of Neurology
Symposium II-2: Apoptosis of neurodegenerative disorders
Cell death protection by anti-apoptotic factor
Ryosuke Takahashi, M. D. , Ph. D.
Lab for Motor System Neurodegeneration RIKEN Brain Science Institute (BSI)
Neurodegenerative disorders including ALS and Parkinson' s disease are characterized by progressive loss of neuronal cell death. Apoptosis, a morphologically and biochemically defined form of cell death caused by active cellular signaling, has been long implicated in neurodegeneration. Recently, the basic molecular mechanism of apoptosis has been elucidated and a subset of systeine proteases called caspases were shown to be the executioner of apoptosis. On the other hand, endogenous caspase inhibitor called inhibitor of apoptosis proteins (IAPs) were also identified. XIAP, the most potent apoptosis inhibitor among human IAPs, is shown to be direct and selective inhibitor for caspase-3, -7 and -9. We have very recently shown that XIAP has ubiquitin ligase activity which promotes the degradation of caspase-3and this protease activity enhances the anti-apoptotic activity of XIAP.
Regarding the involvement of apoptosis in neurodegenerative diseases, several lines of evidence indicated that caspases are involved in the pahtogeneis of ALS and polyglutamine disease, suggesting the effectiveness of anti-apototic therapy forthese diseases. Moreover, caspase-independent programmed cell death is also suggested to be involved in neurodegenerative disorders. Based on these findings, the therapeutic strategy for neurodegenerative disease should include both anti-apoptotic and anti-non-apoptotic cell death treatments.
(CLINICA NEUROL, 41: 1067－1069, 2001)
key words: caspase, mitochondria, IAP, neurodegeneration
(Received: 12-May-01)
