The impact of reactive oxygen species and genetic mitochondrial mutations in Parkinson's disease

Abstract

The exact pathogenesis of Parkinson's disease (PD) is still unknown and proper mechanisms that correspond to the disease remain unidentified. It is understood that PD is age-related; as age increases, the chance of onset responds accordingly. Although there are no current means of curing PD, the understanding of reactive oxygen species (ROS) provides significant insight to possible treatments. Complex I deficiencies of the respiratory chain account for the majority of unfavorable neural apoptosis generation in PD. Dopaminergic neurons are severely damaged as a result of the deficiency. Symptoms such as inhibited cognitive ability and loss of smooth motor function are the results of such impairment. The genetic mutations of Parkinson's related proteins such as PINK1 and LRRK2 contribute to mitochondrial dysfunction which precedes ROS formation. Various pathways are inhibited by these mutations, and inevitably causing neural cell damage. Antioxidants are known to negate the damaging effects of free radical overexpression. This paper expands on the specific impact of mitochondrial genetic change and production of free radicals as well as its correlation to the neurodegeneration in Parkinson's disease.

Keywords: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; CNS; DA; DAT; DAergic; DDC; DMT(1); ELLDOPA; ELO1, ELO2, ELO3; EOP; EP; ER; ERK; ETC; GFAP; GSH; Genetic mutations; L-DOPA; LA; LD; LRRK(2); MAO-B; MPTP; NO; Neurodegeneration; Neuron; Nrf2; OS; PARK7; PARP; PBMCs; PD; PI(3)K; PINK(1); PKG; PUFAs; Parkinson's disease; ROS; SNc; TH; The Earlier versus Later Levodopa Therapy; UPC4; UPC5; cGMP-dependent protein kinase; central nervous system; divalent metal transporter 1; dopadecarboxylase; dopamine; dopamine transporters; dopaminergic; early onset Parkinsonism; electron transport chain; elongase genes; endoplasmic reticulum; erythroid 2-related factor 2; ethyl pyruvate; extracellular signal-regulated kinase; glial fibrillary acidic protein; glutathione; iPSC; induced pluripotent stem cell; l-3,4-dihydroxyphenylalanine; leucine-rich repeat kinase 2; levodopa; lipoic acid; monoamine oxidase B; nitric oxide; oxidative stress; parkinson protein 7; peripheral blood mononuclear cells; phosphoinositol-3 kinase; poly (ADP-ribose) polymerase; polyunsaturated free fatty acids; putative kinase 1; reactive oxygen species; substantia nigra pars compacta; tyrosine hydroxylase; uncoupling protein 4; uncoupling protein 5; α-synuclein; αS.