The Role of Free Radicals in the Aging Brain and Parkinson's Disease: Convergence and Parallelism

被引：169
作者：
Kumar, Hemant [1 ]
Lim, Hyung-Woo [1 ]
More, Sandeep Vasant [1 ]
Kim, Byung-Wook [1 ]
Koppula, Sushruta [1 ]
Kim, In Su [1 ]
Choi, Dong-Kug [1 ]
机构：
[1] Konkuk Univ, Dept Biotechnol, Chungju 380704, South Korea
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2012年 / 13卷 / 08期
关键词：
free radicals; aging; Parkinson's disease; alpha-synuclein; mitochondrial dysfunction; nrf2; AGE-RELATED-CHANGES; GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; HUMAN ALPHA-SYNUCLEIN; MITOCHONDRIAL-DNA DELETIONS; TRANSCRIPTION FACTOR NRF2; SUBSTANTIA-NIGRA NEURONS; EARLY-ONSET PARKINSONISM; NF-KAPPA-B; OXIDATIVE STRESS; REACTIVE OXYGEN;
D O I：
10.3390/ijms130810478
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Free radical production and their targeted action on biomolecules have roles in aging and age-related disorders such as Parkinson's disease (PD). There is an age-associated increase in oxidative damage to the brain, and aging is considered a risk factor for PD. Dopaminergic neurons show linear fallout of 5-10% per decade with aging; however, the rate and intensity of neuronal loss in patients with PD is more marked than that of aging. Here, we enumerate the common link between aging and PD at the cellular level with special reference to oxidative damage caused by free radicals. Oxidative damage includes mitochondrial dysfunction, dopamine auto-oxidation, alpha-synuclein aggregation, glial cell activation, alterations in calcium signaling, and excess free iron. Moreover, neurons encounter more oxidative stress as a counteracting mechanism with advancing age does not function properly. Alterations in transcriptional activity of various pathways, including nuclear factor erythroid 2-related factor 2, glycogen synthase kinase 3 beta, mitogen activated protein kinase, nuclear factor kappa B, and reduced activity of superoxide dismutase, catalase and glutathione with aging might be correlated with the increased incidence of PD.
引用
收藏
页码：10478 / 10504
页数：27
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