Oxidative and nitrative protein modifications in Parkinson's disease

Abstract

Parkinson's disease (PD) is a complex neurodegenerative syndrome likely involving contributions from various factors in individuals including genetic susceptibility, exposure to environmental toxins, and the aging process itself. Increased oxidative stress appears to be a common causative aspect involved in the preferential loss of dopaminergic neurons in a region of the brain prominently affected by the disorder, the substantia nigra (SN). Loss of dopaminergic SN neurons is responsible for the classic clinical motor symptoms associated with PD. Several oxidative and nitrative posttranslational modifications (PTMs) have been identified on proteins pertinent to PD that may affect this or other aspects of disease progression. In this review, we discuss several examples of such PTMs to illustrate their potential consequences in terms of initiation or progression of PD neuropathophysiology.

Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

“…The etiology of sporadic PD is unknown although mitochondrial dysfunction, oxidative and nitrosative stresses have been implicated in the mechanisms associated with PD pathogenesis [80,81].…”

“…Lipid and DNA oxidation were also found to be systemically elevated in PD [82]. Oxidative and nitrative posttranslational modifications have been identified on proteins that may affect the disease progression [81]. This includes increased levels of oxidized protein carbonyls in the SN of PD patients [89,90] and nitration of tyrosine residues within LBs in the PD brain [91,92].…”

Reprint of: Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

“…The etiology of sporadic PD is unknown, although mitochondrial dysfunction and oxidative and nitrosative stresses have been implicated in the mechanisms associated with PD pathogenesis [80,81].…”

“…Lipid and DNA oxidation was also found to be systemically elevated in PD [82]. Oxidative and nitrative posttranslational modifications have been identified on proteins that may affect the disease progression [81]. This includes increased levels of oxidized protein carbonyls in the SN of PD patients [89,90] and nitration of tyrosine residues within LBs in the PD brain [91,92].…”

Oxidative Stress in Neurodegenerative Diseases

“…This decrease is one of the earliest biochemical changes that has been observed in the disease [140][141][142][143], and it results in a selective drop in mitochondrial complex I activity, another hallmark of PD [144]. On the other hand, a substantial rise in SOD levels has been observed in the SN and basal ganglia in PD patients [145], while no change in activities of CAT, GPx, and GR was found compared to agematched controls [145].…”