Parkinson’s Disease—Apoptosis and Dopamine Oxidation

• 作者: James David Adams Jr.
• 来源期刊: 细胞凋亡(英文)
• 学科: 医学
• 关键词: TYROSINE HYDROXYLASE MONOAMINE OXIDASE ALDEHYDE DEHYDROGENASE
• 年，卷（期）: 2012,（1）
• 页码范围: 1-8
• 页数: 8页
• 分类号: R73

摘要

Tyrosine hydroxylase, monoamine oxidase and aldehyde dehydrogenase all form oxygen radicals as part of their mechanisms of action. These oxygen radicals damage dopaminergic neurons in the substantianigra of the midbrain and cause them to die by a process of necrosis or apoptosis. Oxygen radicals quickly abstract hydrogen from DNA forming DNA radicals and causing DNA fragmentation, activation of DNA protective mechanisms, NAD depletion and cell death. Tyrosine hydroxylase is present in all dopaminergic neurons, is involved in the synthesis of dopamine and forms oxygen radicals in a redox mechanism involving its cofactor, tetrahydrobiopterin. Levodopa is used therapeutically in Parkinson’s disease patients since it is a precursor for dopamine, an inhibitor of tyrosine hydroxylase, and prolongs pa-tient’s lives. Monoamine oxidase converts dopamine into 3,4-dihydroxyphenylacetaldehyde and forms oxygen radi-cals.Aldehyde dehydrogenase oxidizes the aldehyde and forms oxygen radicals and 3,4-dihydroxyphenylacetic acid. The treatment of Parkinson’s disease should involveinhibitors of oxygen radical formation in dopaminergic neurons and neuroprotective agents that stimulate DNA repair and prevent cell death.