Imbalance of Lysine Acetylation Contributes to the Pathogenesis of Parkinson’s Disease

Wang, Rui; Sun, Hongyang; Wang, Guanghui; Ren, Haigang

doi:10.3390/ijms21197182

Cited by 31 publications

(27 citation statements)

References 132 publications

(170 reference statements)

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“…Parkinson’s disease (PD), the most common neurodegenerative movement disorder, affects approximately 1% of the population over 60 years old, and its incidence dramatically increases to approximately 5% in the population greater than 85 years of age ( Li and Le, 2020 ; Wang et al, 2020b ). PD is a chronic, irreversible, and complex neurodegenerative disease with several typical motor impairments including resting tremor, bradykinesia, rigidity, and postural imbalance.…”

Section: Introductionmentioning

confidence: 99%

The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson’s Disease

Ren

Zhai

et al. 2021

Front. Aging Neurosci.

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Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, and it is characterized by the selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), as well as the presence of intracellular inclusions with α-synuclein as the main component in surviving DA neurons. Emerging evidence suggests that the imbalance of proteostasis is a key pathogenic factor for PD. Endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and autophagy, two major pathways for maintaining proteostasis, play important roles in PD pathology and are considered as attractive therapeutic targets for PD treatment. However, although ER stress/UPR and autophagy appear to be independent cellular processes, they are closely related to each other. In this review, we focused on the roles and molecular cross-links between ER stress/UPR and autophagy in PD pathology. We systematically reviewed and summarized the most recent advances in regulation of ER stress/UPR and autophagy, and their cross-linking mechanisms. We also reviewed and discussed the mechanisms of the coexisting ER stress/UPR activation and dysregulated autophagy in the lesion regions of PD patients, and the underlying roles and molecular crosslinks between ER stress/UPR activation and the dysregulated autophagy in DA neurodegeneration induced by PD-associated genetic factors and PD-related neurotoxins. Finally, we indicate that the combined regulation of ER stress/UPR and autophagy would be a more effective treatment for PD rather than regulating one of these conditions alone.

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Section: Introductionmentioning

confidence: 99%

The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson’s Disease

Ren

Zhai

et al. 2021

Front. Aging Neurosci.

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“…It was recently demonstrated that the number of tandem repeats and methylation levels of the first intron of SLC6A3 gene might be related to nicotine dependence and a potentially increased tendency to start smoking and an impaired ability to quit [ 55 ]. Another recent study demonstrated that the DNA methylation rates of DRD2 in peripheral leukocytes were reduced in PD patients [ 102 ]. DRD2 is considered a risk factor for PD, and ANKK1/DRD2 genetic region variants have been associated with nicotine dependence in males in a Chinese study [ 56 ].…”

Section: Environmental Impact On Epigenetic Modifications In Pdmentioning

confidence: 99%

Environmental Impact on the Epigenetic Mechanisms Underlying Parkinson’s Disease Pathogenesis: A Narrative Review

et al. 2022

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Parkinson’s disease (PD) is the second most common neurodegenerative disorder with an unclear etiology and no disease-modifying treatment to date. PD is considered a multifactorial disease, since both genetic and environmental factors contribute to its pathogenesis, although the molecular mechanisms linking these two key disease modifiers remain obscure. In this context, epigenetic mechanisms that alter gene expression without affecting the DNA sequence through DNA methylation, histone post-transcriptional modifications, and non-coding RNAs may represent the key mediators of the genetic–environmental interactions underlying PD pathogenesis. Environmental exposures may cause chemical alterations in several cellular functions, including gene expression. Emerging evidence has highlighted that smoking, coffee consumption, pesticide exposure, and heavy metals (manganese, arsenic, lead, etc.) may potentially affect the risk of PD development at least partially via epigenetic modifications. Herein, we discuss recent accumulating pre-clinical and clinical evidence of the impact of lifestyle and environmental factors on the epigenetic mechanisms underlying PD development, aiming to shed more light on the pathogenesis and stimulate future research.

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“…Although the exact mechanism remains unknown, polo-like kinases (PLK) could be responsible for regulating this phosphorylation event in the serine 129 [143]. Apart from phosphorylation, lysine acetylation status of α-synuclein has been involved in the pathogenesis of the disease as well [144]. In addition, this protein modification impairs mitophagy in fibroblasts, as shown for PD patients [145].…”

Section: Dietary Polyphenols and Neurodegenerationmentioning

confidence: 99%

Dietary Polyphenols in Metabolic and Neurodegenerative Diseases: Molecular Targets in Autophagy and Biological Effects

et al. 2021

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Polyphenols represent a group of secondary metabolites of plants which have been analyzed as potent regulators of multiple biological processes, including cell proliferation, apoptosis, and autophagy, among others. These natural compounds exhibit beneficial effects and protection against inflammation, oxidative stress, and related injuries including metabolic diseases, such as cardiovascular damage, obesity and diabetes, and neurodegeneration. This review aims to summarize the mechanisms of action of polyphenols in relation to the activation of autophagy, stimulation of mitochondrial function and antioxidant defenses, attenuation of oxidative stress, and reduction in cell apoptosis, which may be responsible of the health promoting properties of these compounds.

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Imbalance of Lysine Acetylation Contributes to the Pathogenesis of Parkinson’s Disease

Cited by 31 publications

References 132 publications

The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson’s Disease

The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson’s Disease

Environmental Impact on the Epigenetic Mechanisms Underlying Parkinson’s Disease Pathogenesis: A Narrative Review

Dietary Polyphenols in Metabolic and Neurodegenerative Diseases: Molecular Targets in Autophagy and Biological Effects

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