1. A secret that underlies Parkinson's disease: The damaging cycle.
- Author
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Sun F, Deng Y, Han X, Liu Q, Zhang P, Manzoor R, and Ma H
- Subjects
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Aldehydes metabolism, Antiparkinson Agents pharmacology, Antiparkinson Agents therapeutic use, Biogenic Amines metabolism, Drug Design, Gene-Environment Interaction, Humans, Inflammasomes physiology, MicroRNAs genetics, Mitochondria physiology, Mutation, Neuroglia physiology, Oxidative Stress, Oxidopamine toxicity, Parkinson Disease drug therapy, Parkinson Disease immunology, Parkinson Disease metabolism, Protein Aggregation, Pathological, T-Lymphocyte Subsets immunology, alpha-Synuclein genetics, alpha-Synuclein physiology, Models, Neurological, Parkinson Disease physiopathology
- Abstract
Parkinson's disease (PD) is a movement disorder, and its common characteristics include the loss of dopaminergic neurons and the accumulation of a special type of cytoplasmic inclusions called Lewy bodies in the substantia nigra pars compacta, which are more prevalent in the elderly. However, the pathophysiology of PD is still elusive. In this review, we summarized five common factors involved in PD, namely, (i) oxidative stress, (ii) mitochondrial dysfunction, (iii) inflammation, (iv) abnormal α-synuclein, and (v) endogenous neurotoxins, and proposed a hypothesis involving a damaging cycle. Oxidative stress-triggered aldehydes react with biogenic amines to produce endogenous neurotoxins. They cause mitochondrial dysfunction and the formation of inflammasomes, which induce the activation of neuroglial cells and the infiltration of T lymphocytes. The synergistic effect of these processes fosters chronic inflammation and α-synuclein aggregation and further exacerbates the impact of oxidative stress to establish a damaging cycle that eventually results in the degeneration of dopaminergic neurons. This damaging cycle provides an explanation of progressive neuronal death during the pathogenesis of PD and provides new potential targets beneficial for developing new drugs and approaches for clinical neuroprotection., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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