Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, E/CLS-628, Boston, MA 02215, USA.
Parkinsons Dis. 2011;2011:659694. doi: 10.4061/2011/659694. Epub 2011 Apr 27.
A great deal of evidence supports a role for mitochondrial dysfunction in the pathogenesis of Parkinson's disease (PD), although the origin of the mitochondrial dysfunction in PD remains unclear. Expression of mitochondrial DNA (mtDNA) from PD patients in "cybrid" cell lines recapitulates the mitochondrial defect, implicating a role for mtDNA mutations, but the specific mutations responsible for the mitochondrial dysfunction in PD have been difficult to identify. Somatic mtDNA point mutations and deletions accumulate with age and reach high levels in substantia nigra (SN) neurons. Mutations in mitochondrial DNA polymerase γ (POLG) that lead to the accumulation of mtDNA mutations are associated with a premature aging phenotype in "mutator" mice, although overt parkinsonism has not been reported in these mice, and with parkinsonism in humans. Together these data support, but do not yet prove, the hypothesis that the accumulation of somatic mtDNA mutations in SN neurons contribute to the pathogenesis of PD.
大量证据表明线粒体功能障碍在帕金森病 (PD) 的发病机制中起重要作用，尽管 PD 中线粒体功能障碍的起源仍不清楚。将 PD 患者的线粒体 DNA (mtDNA) 在“细胞杂种”细胞系中的表达重现了线粒体缺陷，提示 mtDNA 突变起作用，但导致 PD 中线粒体功能障碍的具体突变一直难以确定。体细胞 mtDNA 点突变和缺失随年龄积累，并在黑质 (SN) 神经元中达到高水平。导致 mtDNA 突变积累的线粒体 DNA 聚合酶 γ (POLG) 突变与“突变体”小鼠中早老表型相关，尽管这些小鼠中未报告明显的帕金森病，而与人类帕金森病相关。这些数据支持，但尚未证明，SN 神经元中线粒体 DNA 体细胞突变的积累导致 PD 发病机制的假说。
