عدم وجود مدرک مربوط به کوتاه شدن تلومر سیاه مغز ماده در بیماری پارکینسون

Telomeres are repetitive tracts of DNA which protect chromosomal integrity. Increased oxidative stress leads to shorter telomeres, which have been associated with several late-onset human diseases. Given independent evidence of oxidative stress and Parkinson's disease (PD), and conflicting reports of the role of telomere length in PD, we measured telomere length in both PD peripheral blood monocytes and in substantia nigra from affected individuals and controls. We confirmed previous findings of a paradoxically longer telomere length in blood from PD patients, but found no difference in telomere length in substantia nigra. Confounding factors provide a likely explanation for the findings in blood, and possibly the reduced frequency of cigarette smoking in PD patients. We conclude that telomere shortening is unlikely to be involved in the pathogenesis of PD.

Telomeres are regions of repetitive DNA that maintain chromosomal integrity by preventing chromosome ends from being recognized as double strand breaks. Short telomeres have been observed in senescent cells, in response to increased oxidative stress and chronic inflammation, leading to the hypotheses that telomere length may be a useful biomarker for late-onset diseases with increased reactive oxygen species production. It is therefore plausible that Parkinson's disease, an age-related neurodegenerative disorder characterized by selective death of dopaminergic neurons in the substantia nigra, is associated with shortened telomere length. Previous studies of telomere length in Parkinson's disease (PD) have reached diametrically opposed conclusions, with one reporting the expected shorter telomere length in PD, and the other significantly longer telomere lengths in PD (Guan et al., 2008; 28 cases and 27 controls; Wang et al., 2008; 96 cases and 172 controls). This study was designed to resolve this controversy, and to determine the pathological relevance of these findings by studying substantia nigra from affected and unaffected individuals. In addition, we compared telomere length to genetic variants of mitochondrial DNA (mtDNA haplogroups) which have been also associated with increased reactive oxygen species production and PD.