Exploring the Role of Ubiquitin–Proteasome System in Parkinson's Disease

Behl, Tapan; Kumar, Sachin; Althafar, Ziyad M.; Sehgal, Aayush; Singh, Sukhbir; Sharma, Neelam; Badavath, Vishnu Nayak; Yadav, Shivangi; Bhatia, Saurabh; Al‐Harrasi, Ahmed; Almoshari, Yosif; Almikhlafi, Mohannad A.; Bungău, Simona

doi:10.1007/s12035-022-02851-1

Cited by 35 publications

(16 citation statements)

References 145 publications

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“…In addition, elevated levels of oxidized coenzyme Q-10 in the CSF are observed in PD patients, indicating oxidative damage in mitochondria [ 138 ]. Oxidative stress and inhibition of complex I are manifested by decreased glutathione levels and inflated iron levels [ 139 ]. PD patients also show a deficiency of mitochondrial complex IV (cytochrome c oxidase).…”

Section: Parkinson’s Diseasementioning

confidence: 99%

Metabolomic Footprint of Disrupted Energetics and Amino Acid Metabolism in Neurodegenerative Diseases: Perspectives for Early Diagnosis and Monitoring of Therapy

et al. 2023

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The prevalence of neurodegenerative diseases (NDs) is increasing due to the aging population and improved longevity. They are characterized by a range of pathological hallmarks, including protein aggregation, mitochondrial dysfunction, and oxidative stress. The aim of this review is to summarize the alterations in brain energy and amino acid metabolism in Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). Based on our findings, we proposed a group of selected metabolites related to disturbed energy or mitochondrial metabolism as potential indicators or predictors of disease. We also discussed the hidden challenges of metabolomics studies in NDs and proposed future directions in this field. We concluded that biochemical parameters of brain energy metabolism disruption (obtained with metabolomics) may have potential application as a diagnostic tool for the diagnosis, prediction, and monitoring of the effectiveness of therapies for NDs. However, more studies are needed to determine the sensitivity of the proposed candidates. We suggested that the most valuable biomarkers for NDs studies could be groups of metabolites combined with other neuroimaging or molecular techniques. To attain clinically applicable results, the integration of metabolomics with other “omic” techniques might be required.

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Section: Parkinson’s Diseasementioning

confidence: 99%

Metabolomic Footprint of Disrupted Energetics and Amino Acid Metabolism in Neurodegenerative Diseases: Perspectives for Early Diagnosis and Monitoring of Therapy

et al. 2023

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“…CMA is a highly selective catabolic process by mediating proteins containing a specific target motif of CMA (KFERQ), dissociated by cytoplasmic chaperones, and composed of lysosome-associated transmembrane protein (LAMP2A) ( Kaushik and Cuervo, 2018 ). In addition to autophagy, the ubiquitin-proteasome system (UPS) is also involved in the degradation and clearance of abnormal protein aggregates in neurodegenerative diseases ( Behl et al, 2022 ). UPS-dependent degradation may be limited to soluble misfolded proteins or small oligomers, which are allowed to enter the P20S catalytic compartment after unfolding ( Scotter et al, 2014 ).…”

Section: Overview Of Autophagymentioning

confidence: 99%

Interaction between autophagy and the NLRP3 inflammasome in Alzheimer’s and Parkinson’s disease

Zhang

Yang

2022

Front. Aging Neurosci.

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Autophagy degrades phagocytosed damaged organelles, misfolded proteins, and various pathogens through lysosomes as an essential way to maintain cellular homeostasis. Autophagy is a tightly regulated cellular self-degradation process that plays a crucial role in maintaining normal cellular function and homeostasis in the body. The NLRP3 inflammasome in neuroinflammation is a vital recognition receptor in innate cellular immunity, sensing external invading pathogens and endogenous stimuli and further triggering inflammatory responses. The NLRP3 inflammasome forms an inflammatory complex by recognizing DAMPS or PAMPS, and its activation triggers caspase-1-mediated cleavage of pro-IL-1β and pro-IL-18 to promote the inflammatory response. In recent years, it has been reported that there is a complex interaction between autophagy and neuroinflammation. Strengthening autophagy can regulate the expression of NLRP3 inflammasome to reduce neuroinflammation in neurodegenerative disease and protect neurons. However, the related mechanism is not entirely clear. The formation of protein aggregates is one of the standard features of Neurodegenerative diseases. A large number of toxic protein aggregates can induce inflammation. In theory, activation of the autophagy pathway can remove the potential toxicity of protein aggregates and delay the progression of the disease. This article aims to review recent research on the interaction of autophagy, NLRP3 inflammasome, and protein aggregates in Alzheimer’s disease (AD) and Parkinson’s disease (PD), analyze the mechanism and provide theoretical references for further research in the future.

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“…Misfolded into amyloid form, involved in Lewy body composition; aggravates mitochondrial dysfunction, causes oxidative stress, activates neuroinflammation, causes or aggravates UPS abnormalities, induces axonal damage [43,44] Oxidative stress Destabilizes nucleic acids; promotes α-synuclein, Parkin aggregation, and proteasome breakdown [45,46] Mitochondrial dysfunction Disruption of mitochondrial dynamics, bioenergetic defects, complex I inhibition, ETC and increased ROS content; mitochondrial protein phosphatase and PTEN-induced PINK1 and Parkin function and induction of neurodegeneration [47,48] autophagy Degradation of misfolded proteins and damaged organelles by lysosomes [49][50][51] Neuroinflammation Promotes alpha-synuclein synthesis and aggregation; induces abnormal innate and adaptive immune responses [52] Microbial-intestinal-brain axis regulatory mechanisms Induces alpha-synuclein misfolding and translocation of alpha-synuclein to the brain; inhibits glial cell activation; produces neuroinflammation [53,54] UPS dysfunction Induced abnormal protein aggregation, striatal damage, mitochondrial autophagy, and increased DNA content [55][56][57] Excitatory neurotoxicity Increased glutamate leads to oxidative stress and excitotoxicity, affecting cell viability and contributing to neuronal death [58,59] Genetic factors Genetic mutations [60,61] Environmental risk factors Associated with pesticide and heavy metal exposure, rural life, agricultural occupations, head trauma, melanoma, dairy consumption, type 2 diabetes, etc., with no conclusive mechanism [62][63][64] ETC = electron transport chain, ROS = reactive oxygen species, UPS = Ubiquitin -proteasome system.…”

Section: Abnormal Aggregation Of α-Synucleinmentioning

confidence: 99%

Exploring the relationship between novel Coronavirus pneumonia and Parkinson’s disease

Liang

2022

Medicine

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The hypothesis is that there is 0a relationship between Parkinson's disease and coronavirus disease 2019 . By summarizing the pathogenesis of Parkinson's disease and COVID-19 and the impact of COVID-19 on the central nervous system, the relationship between Parkinson's disease and COVID-19 was analyzed, including whether Parkinson's disease is a predisposition factor for COVID-19 and whether COVID-19 causes the occurrence of Parkinson's disease. Discuss the impact of COVID-19 on patients with Parkinson's disease, including symptoms and life impact. To summarize the principles, goals and methods of home rehabilitation for Parkinson's disease patients during COVID-19. Through the analysis of this paper, it is believed that COVID-19 may cause Parkinson's disease. Parkinson's disease has the condition of susceptibility to COVID-19, but this conclusion is still controversial.Abbreviations: ACE2 = angiotensin-converting enzyme receptor 2, CNS = central nervous system, COVID-19 = coronavirus disease 2019, DDC = dopamine decarboxylase, PD = Parkinson's disease, SARS-CoV-2 = severe acute respiratory syndrome Coronavirus-2.

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Exploring the Role of Ubiquitin–Proteasome System in Parkinson's Disease

Cited by 35 publications

References 145 publications

Metabolomic Footprint of Disrupted Energetics and Amino Acid Metabolism in Neurodegenerative Diseases: Perspectives for Early Diagnosis and Monitoring of Therapy

Metabolomic Footprint of Disrupted Energetics and Amino Acid Metabolism in Neurodegenerative Diseases: Perspectives for Early Diagnosis and Monitoring of Therapy

Interaction between autophagy and the NLRP3 inflammasome in Alzheimer’s and Parkinson’s disease

Exploring the relationship between novel Coronavirus pneumonia and Parkinson’s disease

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