Neuroprotective strategies for treatment of lesions produced by mitochondrial toxins: implications for neurodegenerative diseases

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• 作者：Schulz ; J. B. ; Matthews ; R. T. ; Henshaw ; D. R. ; Beal ; M. F.
• 关键词：Parkinson's disease ; Huntington's disease ; mitochondria ; free radicals ; excitotoxicity ; coenzyme Q₁₀
• 刊名：Neuroscience
• 出版年：1996
• 出版时间：April, 1996
• 年：1996
• 卷：71
• 期：4
• 页码：1043-1048
• 全文大小：688 K

文摘

Neuronal death in neurodegenerative diseases may involve energy impairment leading to secondary excitotoxicity, and free radical generation. Potential therapies for the treatment of neurodegenerative diseases therefore include glutamate release blockers, excitatory amino acid receptor antagonists, agents that improve mitochondrial function, and free radical scavengers. In the present study we examined whether these strategies either alone or in combination had neuroprotective effects against striatal lesions produced by mitochondrial toxins. The glutamate release blockers lamotrigine and BW1003C87 significantly attenuated lesions produced by intrastriatal administration of 1-methyl-4-phenylpyridinium. Lamotrigine significantly attenuated lesions produced by systemic administration of 3-nitropropionic acid. Memantine, an N-methyl-d-aspartate antagonist, protected against malonate induced striatal lesions. We previously found that coenzyme Q₁₀ and nicotinamide, and the free radical spin trap n-tert-butyl-α-(2-sulfophenyl)-nitrone (S-PBN) dose-dependently protect against lesions produced by intrastriatal injection of malonate. In the present study we found that the combination of MK-801 (dizocipiline) with coenzyme Q₁₀ exerted additive neuroprotective effects against malonate. Lamotrigine with coenzyme Q₁₀ was more effective than coenzyme Q₁₀ alone. The combination of nictotinamide with S-PBN was more effective than nicotinamide alone.