Lipid-mediated oxidative stress and inflammation in the pathogenesis of Parkinson's disease

Tahira Farooqui, Akhlaq A Farooqui, Tahira Farooqui, Akhlaq A Farooqui

Abstract

Parkinson's disease (PD) is a neurodegenerative movement disorder of unknown etiology. PD is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, depletion of dopamine in the striatum, abnormal mitochondrial and proteasomal functions, and accumulation of α-synuclein that may be closely associated with pathological and clinical abnormalities. Increasing evidence indicates that both oxidative stress and inflammation may play a fundamental role in the pathogenesis of PD. Oxidative stress is characterized by increase in reactive oxygen species (ROS) and depletion of glutathione. Lipid mediators for oxidative stress include 4-hydroxynonenal, isoprostanes, isofurans, isoketals, neuroprostanes, and neurofurans. Neuroinflammation is characterized by activated microglial cells that generate proinflammatory cytokines, such as TNF-α and IL-1β. Proinflammatory lipid mediators include prostaglandins and platelet activating factor, together with cytokines may play a prominent role in mediating the progressive neurodegeneration in PD.

Figures

Figure 1
Figure 1
Potential factors and events associated with the pathogenesis of PD.
Figure 2
Figure 2
Generation of ROS, activation of NF-κB, redox status, and gene expression in Parkinson's disease. (1) NADPH oxidase; (2) superoxide dismutase; (3) catalase; (4) glutathione peroxidase; (5) glutathione reductase; cytosolic phospholipase A2 (cPLA2); secretory phospholipase A2 (sPLA2); cyclooxygenase-2 (COX), lipoxygenase (LOX); SOD; nitric oxide synthase (NOS); cytokines, TNF-α and IL-1β; reduced glutathione (GSH); oxidized glutathione (GSSG) and hydrogen peroxide (H2O2). Increase in oxidative stress-mediated expression of NF-κB induces transcription of sPLA2. COX-2, NOS, and SOD in the nucleus as well as proinflammatory cytokines (TNF-α and IL-1β) that further upregulate activities of cPLA2, sPLA2, NOS through a positive loop mechanism in cytoplasm and neural membranes.
Figure 3
Figure 3
Chemical structures of biomarkers for oxidative stress.

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