DiDonato S, Zeviani M, Giovannini P, Savarese N, Rimoldi M, Mariotti C, Girotti F, Caraceni T
Division of Biochemistry and Genetics, Istituto Nazionale Neurologico C. Besta, Milan, Italy.
Neurology. 1993 Nov;43(11):2262-8. doi: 10.1212/wnl.43.11.2262.
There are several reports of a defect of complex I in the substantia nigra (SN) of Parkinson's disease (PD) patients. To evaluate whether this is specific to dopaminergic neurons or the phenotypically relevant consequence of a widespread failure of the mitochondrial oxidative phosphorylation (OXPHOS) system, we measured respiratory enzyme activities in muscle homogenates from 16 PD patients and eight age-matched controls, and in muscle isolated mitochondria of six PD patients and six age-matched controls. We found no difference between the PD and control groups. In addition, we detected, by polymerase chain reaction, the mitochondrial DNA (mtDNA) "common deletion" (CD) in muscle specimens of 14 of 17 PD patients, but we obtained similar results in age-matched controls. In both groups, the amount of CD-specific deleted (delta) mtDNA ranged from 0.0% to 0.1%. Our data suggest that PD cannot be attributed to a multisystem decline of mitochondrial OXPHOS, and that lesions of muscle mtDNA in PD are likely due to normal aging. However, there was a remarkable accumulation of delta mtDNA in the SN of a PD patient and an age-matched control, suggesting that the SN is exquisitely sensitive to age-dependent damage of the mitochondrial genome.
有几份报告称帕金森病（PD）患者黑质（SN）中存在复合体I缺陷。为了评估这是否特定于多巴胺能神经元，还是线粒体氧化磷酸化（OXPHOS）系统广泛功能衰竭的表型相关后果，我们测量了16名PD患者和8名年龄匹配对照者肌肉匀浆中的呼吸酶活性，以及6名PD患者和6名年龄匹配对照者肌肉分离线粒体中的呼吸酶活性。我们发现PD组和对照组之间没有差异。此外，我们通过聚合酶链反应在17名PD患者中的14名患者的肌肉标本中检测到线粒体DNA（mtDNA）“常见缺失”（CD），但在年龄匹配的对照者中也得到了类似结果。在两组中，CD特异性缺失（δ）mtDNA的量范围为0.0%至0.1%。我们的数据表明，PD不能归因于线粒体OXPHOS的多系统衰退，并且PD患者肌肉mtDNA的损伤可能是由于正常衰老。然而，一名PD患者和一名年龄匹配对照者的SN中存在显著的δmtDNA积累，表明SN对线粒体基因组的年龄依赖性损伤极为敏感。
