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α-synucleinopathy exerts sex-dimorphic effects on the multipurpose DNA repair/redox protein APE1 in mice and humans.

Journal Article Prog Neurobiol · September 2022 Lewy body disorders are characterized by oxidative damage to DNA and inclusions rich in aggregated forms of α-synuclein. Among other roles, apurinic/apyrimidinic endonuclease 1 (APE1) repairs oxidative DNA damage, and APE1 polymorphisms have been linked to ... Full text Link to item Cite

A Connection Between DNA Repair Protein APE1, Alpha-Synucleinopathy, and Biological Sex in Rodents and Humans

Journal Article Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology · May 1, 2022 Lewy body disorders are characterized by proteostatic and redox disequilibrium, leading to deposition of α-synuclein in hallmark inclusions and oxidative damage to DNA. One common pathway for repair of oxidative DNA damage is base excision repair (BER), wh ... Full text Cite

Acoustofluidic multimodal diagnostic system for Alzheimer's disease.

Journal Article Biosens Bioelectron · January 15, 2022 Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative brain disorder that affects tens of millions of older adults worldwide and has significant economic and societal impacts. Despite its prevalence and severity, early diagnosis of A ... Full text Link to item Cite

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

Journal Article J Neurosci Res · January 2021 Parkinson's disease (PD) is the most common movement neurodegenerative disorder. Although our understanding of the underlying mechanisms of pathogenesis in PD has greatly expanded, this knowledge thus far has failed to translate into disease-modifying ther ... Full text Link to item Cite

Somatic Mutations in LRRK2 Identify a Subset of Invasive Mammary Carcinomas Associated with High Mutation Burden.

Journal Article Am J Pathol · December 2020 Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial Parkinson disease. Although LRRK2-related Parkinson disease patients have a heightened risk of certain nonskin cancers, including breast cancer, it is unknown ... Full text Link to item Cite

Mitochondrial DNA damage as a potential biomarker of LRRK2 kinase activity in LRRK2 Parkinson's disease.

Journal Article Sci Rep · October 14, 2020 Leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for the treatment of Parkinson's disease (PD) and LRRK2 kinase inhibitors are currently being tested in early phase clinical trials. In order to ensure the highest chance of success, a ... Full text Link to item Cite

Age-related declines in α-Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration.

Journal Article Nat Commun · November 19, 2018 While young muscle is capable of restoring the original architecture of damaged myofibers, aged muscle displays a markedly reduced regeneration. We show that expression of the "anti-aging" protein, α-Klotho, is up-regulated within young injured muscle as a ... Full text Link to item Cite

Evidence for Compartmentalized Axonal Mitochondrial Biogenesis: Mitochondrial DNA Replication Increases in Distal Axons As an Early Response to Parkinson's Disease-Relevant Stress.

Journal Article J Neurosci · August 22, 2018 Dysregulation of mitochondrial biogenesis is implicated in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). However, it is not clear how mitochondrial biogenesis is regulated in neurons, with their unique compartmentalized a ... Full text Link to item Cite

LRRK2 activation in idiopathic Parkinson's disease.

Journal Article Sci Transl Med · July 25, 2018 Missense mutations in leucine-rich repeat kinase 2 (LRRK2) cause familial Parkinson's disease (PD). However, a potential role of wild-type LRRK2 in idiopathic PD (iPD) remains unclear. Here, we developed proximity ligation assays to assess Ser1292 phosphor ... Full text Link to item Cite

Newly Revised Quantitative PCR-Based Assay for Mitochondrial and Nuclear DNA Damage.

Journal Article Curr Protoc Toxicol · May 2018 Given the crucial role of DNA damage in human health and disease, it is important to be able to accurately measure both mitochondrial and nuclear DNA damage. This article describes a method based on a long-amplicon quantitative PCR-based assay that does no ... Full text Link to item Cite

DNA damage by oxidative stress: Measurement strategies for two genomes

Journal Article Current Opinion in Toxicology · February 1, 2018 DNA damage is any modification to the structure of DNA that alters its coding properties and/or interferes with cell processes. One major consequence of oxidative stress is DNA damage, which include base modifications, abasic sites, and strand breaks. A wi ... Full text Cite

RAD52 is required for RNA-templated recombination repair in post-mitotic neurons.

Journal Article J Biol Chem · January 26, 2018 It has been long assumed that post-mitotic neurons only utilize the error-prone non-homologous end-joining pathway to repair double-strand breaks (DSBs) associated with oxidative damage to DNA, given the inability of non-replicating neuronal DNA to utilize ... Full text Link to item Cite

Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson's disease.

Journal Article Neurobiol Dis · January 2018 Parkinson's disease (PD) is a complex, chronic and progressive neurodegenerative disease. While the etiology of PD is likely multifactorial, the protein α-synuclein is a central component to the pathogenesis of the disease. However, the mechanism by which ... Full text Link to item Cite

LRRK2 G2019S-induced mitochondrial DNA damage is LRRK2 kinase dependent and inhibition restores mtDNA integrity in Parkinson's disease.

Journal Article Hum Mol Genet · November 15, 2017 Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with increased risk for developing Parkinson's disease (PD). Previously, we found that LRRK2 G2019S mutation carriers have increased mitochondrial DNA (mtDNA) damage and after zinc finger nuc ... Full text Link to item Cite

Synthetic alpha-synuclein fibrils cause mitochondrial impairment and selective dopamine neurodegeneration in part via iNOS-mediated nitric oxide production.

Journal Article Cell Mol Life Sci · August 2017 Intracellular accumulation of α-synuclein (α-syn) are hallmarks of synucleinopathies, including Parkinson's disease (PD). Exogenous addition of preformed α-syn fibrils (PFFs) into primary hippocampal neurons induced α-syn aggregation and accumulation. Like ... Full text Link to item Cite

Editor's Highlight: Base Excision Repair Variants and Pesticide Exposure Increase Parkinson's Disease Risk.

Journal Article Toxicol Sci · July 1, 2017 Exposure to certain pesticides induces oxidative stress and increases Parkinson's disease (PD) risk. Mitochondrial DNA (mtDNA) damage is found in dopaminergic neurons in idiopathic PD and following pesticide exposure in experimental models thereof. Base ex ... Full text Link to item Cite

Extensive uptake of α-synuclein oligomers in astrocytes results in sustained intracellular deposits and mitochondrial damage.

Journal Article Mol Cell Neurosci · July 2017 The presence of Lewy bodies, mainly consisting of aggregated α-synuclein, is a pathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The α-synuclein inclusions are predominantly found in neurons, but also appear frequently ... Full text Link to item Cite

Toxin-Mediated Complex I Inhibition and Parkinson’s Disease

Chapter · October 13, 2016 Featured Publication This volume brings together various theories of how aberrations in mitochondrial function and morphology contribute to neurodegeneration in idiopathic and familial forms of Parkinson’s disease. ...