Exp Neurobiol.  2013 Mar;22(1):11-17. 10.5607/en.2013.22.1.11.

Role of Oxidative Stress in Parkinson's Disease

• Hwang O

• KMID: 2165436
• DOI: http://doi.org/10.5607/en.2013.22.1.11

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder associated with a selective loss of the dopamine(DA)rgic neurons in the substantia nigra pars compacta and the degeneration of projecting nerve fibers in the striatum. Because there is currently no therapy that delays the neurodegenerative process, modification of the disease course by neuroprotective therapy is an important unmet clinical need. Toward this end, understanding cellular mechanisms that render the nigral neurons particularly vulnerable have been a subject of intensive research. Increasing evidence suggests that oxidative stress plays a major role. The metabolism of DA itself contributes to oxidative stress, resulting in modification of intracellular macromolecules whose functions are important for cell survival. Mitochondrial dysfunction and the consequent increase in reactive oxygen species also trigger a sequence of events that leads to cell demise. In addition, activated microglia produce nitric oxide and superoxide during neuroinflammatory responses, and this is aggravated by the molecules released by damaged DAergic neurons such as alpha-synuclein, neuromelanin and matrix metalloproteinase-3. Ways to reduce oxidative stress therefore can provide a therapeutic strategy. NAD(P)H:quinone reductase (NQO1) and other antioxidant enzymes, whose gene expression are commonly under the regulation of the transcription factor Nrf2, can serve as target proteins utilized toward development of disease-modifying therapy for PD.

Keyword

Parkinson's disease; dopamine; oxidative stress; neuroinflammation; MMP-3; NQO1

MeSH Terms

alpha-Synuclein
Cell Survival
Dopamine
Gene Expression
Melanins
Microglia
Movement Disorders
Nerve Fibers
Neurons
Nitric Oxide
Oxidative Stress
Oxidoreductases
Parkinson Disease
Proteins
Reactive Oxygen Species
Substantia Nigra
Superoxides
Transcription Factors
Dopamine
Melanins
Nitric Oxide
Oxidoreductases
Proteins
Reactive Oxygen Species
Superoxides
Transcription Factors
alpha-Synuclein