|
|||||
|
|
The impact of reactive oxygen species and genetic mitochondrial mutations in Parkinson's disease |
|
| Authors: | Li Zuo Michael S Motherwell |
| Institution: | 1. Molecular Physiology and Biophysics Laboratory, Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA;2. Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, Biophysics Graduate Program, The Ohio State University College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA |
| 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: | αS α-synuclein CNS central nervous system DA dopamine DAergic dopaminergic DAT dopamine transporters DDC dopadecarboxylase DMT1 divalent metal transporter 1 ELLDOPA The Earlier versus Later Levodopa Therapy ELO1 ELO2 ELO3 elongase genes EOP early onset Parkinsonism EP ethyl pyruvate ER endoplasmic reticulum ERK extracellular signal-regulated kinase ETC electron transport chain GFAP glial fibrillary acidic protein GSH glutathione iPSC induced pluripotent stem cell LA lipoic acid LD levodopa LRRK2 leucine-rich repeat kinase 2 L-DOPA l-3 4-dihydroxyphenylalanine MAO-B monoamine oxidase B MPTP 1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine NO nitric oxide Nrf2 erythroid 2-related factor 2 OS oxidative stress PD Parkinson's disease PARK7 parkinson protein 7 PARP poly (ADP-ribose) polymerase PBMCs peripheral blood mononuclear cells PINK1 putative kinase 1 PI3K phosphoinositol-3 kinase PKG cGMP-dependent protein kinase PUFAs polyunsaturated free fatty acids ROS reactive oxygen species SNc substantia nigra pars compacta TH tyrosine hydroxylase UPC4 uncoupling protein 4 UPC5 uncoupling protein 5 |
| 本文献已被 ScienceDirect 等数据库收录！ | |