DNA damage and repair in Parkinson's disease: Recent advances and new opportunities

Gonzalez‐Hunt, Claudia P.; Sanders, Laurie H.

doi:10.1002/jnr.24592

Cited by 38 publications

(38 citation statements)

References 102 publications

(113 reference statements)

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“…We observed lower expression of ARP2/3 in PD vs. HC. Animal studies prove that accumulation of alpha-synuclein can induce DNA single-strand and double-strand breaks [ 48 , 49 ], which are not limited to the central nervous system. We hypothesize that lower expression of the Arp2/3 complex may reflect an inefficient repair mechanism of DNA damage in the PD cohort.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profile of Saliva in Parkinson’s Disease Patients: A Proof of Concept Study

et al. 2021

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder. It affects many organs. Lewy bodies—a histopathological “hallmark” of PD—are detected in about 75% of PD submandibular gland samples. We hypothesize that saliva can be a source of biomarkers of PD. The aim of the study was to evaluate and compare the salivary proteome of PD patients and healthy controls (HC). Salivary samples from 39 subjects (24 PD patients, mean age 61.6 ± 8.2; 15 HC, mean age 60.9 ± 6.7) were collected. Saliva was collected using RNA-Pro-Sal kits. Label-free LC-MS/MS mass spectrometry was performed to characterize the proteome of the saliva. IPA analysis of upstream inhibitors was performed. A total of 530 proteins and peptides were identified. We observed lower concentrations of S100-A16, ARP2/3, and VPS4B in PD group when compared to HC. We conclude that the salivary proteome composition of PD patients is different than that of healthy controls. We observed a lower concentration of proteins involved in inflammatory processes, exosome formation, and adipose tissue formation. The variability of expression of proteins between the two groups needs to be considered.

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Section: Discussionmentioning

confidence: 99%

Proteomic Profile of Saliva in Parkinson’s Disease Patients: A Proof of Concept Study

et al. 2021

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“…Accumulation of DNA lesions and defects in DNA damage repair have been observed in the nervous system of individuals affected by neurodegeneration. Over the last two decades, mounting evidence has indicated the potential contribution of genome maintenance mechanisms to the onset and progression of neurological degenerative diseases [52][53][54][55]. Specifically, mutations predisposing to ALS were shown to alter DDR activation, impair repair, and increase DNA damage accumulation in motor neurons derived from patients induced pluripotent stem cells and in spinal cord tissues [56][57][58].…”

Section: Trends Trends In In Genetics Geneticsmentioning

confidence: 99%

DNA Damage Triggers a New Phase in Neurodegeneration

et al. 2021

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“…Then we performed the functional analyses of GO enrichment and Reactome pathways based on the genes in the ceRNA network and identified not only numerous enriched terms related to PD, including autophagy and vesicles organization, but also plenty of pathways, including DNA Repair and vesicles transport between Golgi and ER. In short, the functional analyses of the ceRNA network focused on three aspects including autophagy, DNA repair and vesicle transport, all of which take part in the pathogenesis of PD (25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Identifying a Comprehensive ceRNA Network to Reveal Novel Targets for the Pathogenesis of Parkinson's Disease

et al. 2020

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Parkinson's disease (PD) is the second commonest progressive neurodegenerative disease worldwide. Increasing evidence reveals that non-coding RNAs play roles in the pathophysiological process of PD. The notion called competing endogenous RNAs (ceRNAs) network is used to describe the roles of non-coding RNAs. According to this theory, long non-coding RNAs (lncRNAs) act as microRNAs (miRNAs) sponges by miRNA response elements or miRNA binding sites to control the availability of endogenous miRNA for binding to their target mRNAs. This study aimed to construct a ceRNA network in PD, which might have the potential to clarify the pathogenesis of PD. We investigated differential expression (DE) lncRNAs and mRNAs in substantia nigra array data GSE7621 between PD patients and healthy controls from the Gene Expression Omnibus database. And we used starBase 2.0 and miRWalk 2.0 databases to predict miRNAs that have interactions with DElncRNAs and DEmRNAs. Based on DElncRNAs, DEmRNAs and predicted miRNAs, two ceRNA networks were constructed. The first one was based on lncRNA-miRNA interactions and miRNA-mRNA interactions that shared the same miRNAs that we predicted, on which function annotation and PPI analysis were performed to identify hub genes. Hereby the second ceRNA network was generated to explore the core section in the first ceRNA network and was validated in external datasets. As a result, we identified 31 DE lncRNAs and 1,828 DEmRNAs, and finally constructed the first ceRNA network associated with PD, including 9 lncRNAs, 18 miRNAs, and 185 mRNAs. mRNAs in the first ceRNA network focused on autophagy, DNA repair and vesicle transport, which were critical pathological processes in PD. Nineteen hub genes in the first ceRNA network identified through PPI analysis, the second ceRNA network was constructed to annotate the core part of the first one. Moreover, the core subnetwork was validated in external datasets, of which several nodes including FBXL7, PTBP2, and lncRNA NEAT1 were verified. In conclusion, a ceRNA network was constructed based on the differential expression profiles of whole substantia nigra tissues of normal and PD patients, and the network was subsequently identified which revealed its association with autophagy, DNA repair and vesicle transport. The core subnetwork of the ceRNA network was identified and validated in external data. Our findings offered novel insights into the roles of ceRNAs in the pathogenesis of PD and provided promising diagnostic biomarkers.

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DNA damage and repair in Parkinson's disease: Recent advances and new opportunities

Cited by 38 publications

References 102 publications

Proteomic Profile of Saliva in Parkinson’s Disease Patients: A Proof of Concept Study

Proteomic Profile of Saliva in Parkinson’s Disease Patients: A Proof of Concept Study

DNA Damage Triggers a New Phase in Neurodegeneration

Identifying a Comprehensive ceRNA Network to Reveal Novel Targets for the Pathogenesis of Parkinson's Disease

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