Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease

GS Gaki, AG Papavassiliou - Neuromolecular medicine, 2014 - Springer
Neuromolecular medicine, 2014Springer
Parkinson's disease is the second most common neurodegenerative movement disorder;
however, its etiology remains elusive. Nevertheless, in vivo observations have concluded
that oxidative stress is one of the most common causes in the pathogenesis of Parkinson's
disease. It is known that mitochondria play a crucial role in reactive oxygen species-
mediated pathways, and several gene products that associate with mitochondrial function
are the subject of Parkinson's disease research. The PTEN-induced kinase 1 (PINK1) …
Abstract
Parkinson’s disease is the second most common neurodegenerative movement disorder; however, its etiology remains elusive. Nevertheless, in vivo observations have concluded that oxidative stress is one of the most common causes in the pathogenesis of Parkinson’s disease. It is known that mitochondria play a crucial role in reactive oxygen species-mediated pathways, and several gene products that associate with mitochondrial function are the subject of Parkinson’s disease research. The PTEN-induced kinase 1 (PINK1) protects cells from mitochondrial dysfunction and is linked to the autosomal recessive familial form of the disease. PINK1 is a key player in many signaling pathways engaged in mitophagy, apoptosis, or microglial inflammatory response and is induced by oxidative stress. Several proteins participate in mitochondrial networks, and they are associated with PINK1. The E3 ubiquitin ligase Parkin, the protease presenilin-associated rhomboid-like serine protease, the tyrosine kinase c-Abl, the protein kinase MARK2, the protease HtrA2, and the tumor necrosis factor receptor-associated protein 1 (TRAP1) provide different steps of control in protection against oxidative stress. Furthermore, environmental toxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, have been identified as contributors to parkinsonism by increasing oxidative stress in dopaminergic neurons. The present review discusses the mechanisms and effects of oxidative stress, the emerging concept of the impact of environmental toxins, and a possible neuroprotective role of the antioxidant astaxanthin in various neurodegenerative disorders with particular emphasis in Parkinson’s disease.
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