Free Radicals, Oxidative Stress and Oxidative Damage in Parkinson's Disease

Parkinson’s disease (PD) is an adult-onset disease of unknown etiology, with a prevalence of 0.3% in the entire population, affecting more than 1% of humans over 60 years of age. Primary degeneration occurs in pigmented dopamine-containing neurons in the pars compacta of the substantia nigra, with projections to the striatum and typical motor signs that appear with a loss of 60% of the dopaminergic neurons of the brain area. While 90-95% of PD cases have no known genetic basis, approximately 5-10% arises from inherited mutations (Farooqui & Farooqui, 2011). While the actual physiopathology of PD remains uncertain, it is currently suggested that the molecular mechanism of the vulnerability of dopaminergic neurons in the substantia nigra involves monoamine oxidase-mediated abnormal dopamine metabolism, hydrogen peroxide generation, and abnormal mitochondrial and proteosomal dysfunctions along with microglia cell activation which may be closely associated with neurodegenerative process. The loss of dopaminergic neurons in the substantia nigra may be related to resting tremor, rigidity, bradykinesia, postural instability, and gait disturbance in PD patients. Also associated with PD neuropathology are disrupted iron homeostasis, intracellular deposition of proteins in Lewy bodies, and oxidative stress and neuronal damage. PD is considered the paradigm of -synucleinopathies within the spectrum of neurodegenerative diseases that exhibit -synuclein in cytosolic protein aggregates (Navarro et al., 2009). There is evidence that oxidative stress participates in the neurodegeneration (Lustig et al., 1993; Famulari et al., 1996; Repetto et al., 1999; Fiszman et al., 2003; Domínguez et al., 2008); neutrophils express a primary alteration of nitric oxide release in PD patients, where reactive oxygen species and oxidative stress parameters are more probably related to the evolution of PD (Gatto et al., 1996; Gatto et al., 1997; Repetto & Llesuy, 2004). Peripheral markers of oxidative stress in red blood cells of neurological patients could be a reflection of the brain condition and suggests that oxygen free radicals are partially responsible for the damage observed in PD living patients (Serra et al., 2001; Repetto, 2008). Other reports suggest that mitochondrial dysfunction and impairment of the respiratory complexes are associated with the neuronal loss (Boveris & Navarro, 2008). Moreover, increased mDNA deletions were recognized in nigral neurons in PD (Bender et al., 2006).