Parkinson's Disease: Cross-Talk Between Environmental Factors and Gene Defects

Publisher Summary This chapter reviews that the environmental contributions to Parkinson's disease (PD) indicate that common features of damage caused by environmental toxins include the disruption of mitochondrial respiration and ensuing energy deficits. This energy deficiency can lead either directly or indirectly via the production of damaging free radicals, to abnormal regulation of protein production and destruction, which may underlie the characteristic cell death in PD. It discusses that inflammation resulting directly from toxin exposure contributes to the ultimate dopamine denervation and that such degeneration might trigger further inflammation and damage DNA through the release of dangerous radicals, in agreement with the multiple hit hypothesis that is widely accepted by PD researchers. The chapter reviews that another attractive proposition for environmental-genetic interactions in PD is that the toxic process itself can induce alterations in an individual's DNA, particularly since mitochondrial DNA would seem to be particularly at risk to this form of damage. It seems likely that PD is multifactorial and does not reflect the same causes in all sufferers. In some, a single gene mutation results in onset of the (familial) condition, in others accidental exposure to a toxin in the environment is sufficient to trigger the (sporadic) illness. In both cases, the patients show a similar pathology, which includes abnormal metabolism and dysfunctional handling of proteins. Finally, it concludes that similarities exist between the pathology of normal aging and PD because both processes involve the more vulnerable parts of the mitochondrial genome and mitochondrial function.