Brain Mitochondrial Dysfunction and Complex I Syndrome in Parkinson´s Disease

VALDEZ LB; BANDEZ MJ; NAVARRO A; BOVERIS A

Etiology and Pathophysiology of Parkinson's Disease

InTech

Lugar: 978-953-307-462-7; Año: 2011; p. 317 - 328

Complex factors contribute to the appearance of Parkinson’s disease (PD), but with constant mitochondrial involvement and a decreased capacity to produce energy (ATP) at the affected brain areas. There are two interdependent conditions in PD: brain mitochondrial dysfunction and brain mitochondrial oxidative damage. Mitochondrial dysfunction and reduced complex I activity have been recognized in substantia nigra and in frontal cortex in PD patients. Experimental models of PD have been developed for mice and rats by the use of MPPT and rotenone. The models produce a similar mitochondrial damage to the one in PD patients in mitochondria isolated from corpora striata and brain cortex. The molecular mechanism involved in the inactivation of complex I is likely accounted by the sum of reactions with free radical intermediates of the lipid peroxidation process, amine-aldehyde adduction reactions and ONOO- mediated reactions. The inhibitory effects on complex I lead synergistically to denaturation of the protein structure and to further increases of O2- and ONOO- production at the vicinity of complex I. An adaptive response in PD patients has been described with increases in mtNOS activity, mitochondrial mass and mitochondrial biogenesis. Mitochondrial dysfunction in the human frontal cortex is to be considered a factor contributing to impaired cognition in PD.