Oxidative and inflammatory pathways in Parkinson's disease.
Parkinson's disease (PD) is the second most prevalent age-related neurodegenerative disease with physiological manifestations including tremors, bradykinesia, abnormal postural reflexes, rigidity and akinesia and pathological landmarks showing losses of dopaminergic neurons in the substantia nigra. Although the etiology of PD has been intensively pursued for several decades, biochemical mechanisms and genetic and epigenetic factors leading to initiation and progression of the disease remain elusive. Environmental toxins including (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) MPTP, paraquat and rotenone have been shown to increase the risk of PD in humans. Oxidative stress remains the leading theory for explaining progression of PD. Studies with cell and animal models reveal oxidative and inflammatory properties of these toxins and their ability to activate glial cells which subsequently destroy neighboring dopaminergic neurons. This review describes pathological effects of neurotoxins on cells and signaling pathways for production of reactive oxygen species (ROS) that underline the pathophysiology of PD.
Miller
Rebecca L
RL
Department of Medical Pharmacology and Physiology, University of Missouri - Columbia, Columbia, MO, 65212, USA.
James-Kracke
Marilyn
M
Sun
Grace Y
GY
Sun
Albert Y
AY
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000818:Animals; D006540:Herbicides / Q000009:adverse effects; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000009:adverse effects; D017628:Microglia / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D016627:Oxidopamine / Q000009:adverse effects; D010269:Paraquat / Q000009:adverse effects; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D020734:Parkinsonian Disorders / Q000209:etiology; D011493:Protein Kinase C / Q000378:metabolism; D012402:Rotenone / Q000009:adverse effects
D006540:Herbicides; D008070:Lipopolysaccharides; D009498:Neurotoxins; D012402:Rotenone; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D010269:Paraquat