ArticleNPJ Parkinson's disease2024
G2019S selective LRRK2 kinase inhibitor abrogates mitochondrial DNA damage.
Article in NPJ Parkinson's disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 25 citations in OpenAlex.
- Intranasal drug delivery to the brain for neurodegenerative diseases: Current efforts and challenges in delivery platforms and modeling.Advanced drug delivery reviews · 2026Review
- Article
- VPS35 mutation inhibits PINK1/parkin-mediated mitophagy via increased LRRK2 kinase activity.Brain : a journal of neurology · 2026Article
- Mitochondrial Fission and Fusion Disorders and Autophagy Abnormalities in Parkinson's Disease.Neurochemical research · 2026Review
- Discovery of multitargeting single agents as a novel route to the potential treatment of neurodegenerative diseases.Bioorganic & medicinal chemistry letters · 2026Article
- Rab12 is a regulator of mitophagy and mitochondrial homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Parkinson's-Linked LRRK2 and GBA1 Mutations Modulate the Peripheral Immune Response to Pseudomonas aeruginosa.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Parkinson's disease linked LRRK2 G2019S drives oxidative nuclear DNA damage and PARP1 hyperactive signaling.bioRxiv : the preprint server for biology · 2026Article
- Precision prevention for neurodegenerative diseases: lessons learnt from Alzheimer's disease translated into perspectives for Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Multilayered interplay between the cGAS-STING pathway and autophagy.Autophagy reports · 2026Review
- LRRK2 kinase-mediated accumulation of lysosome-associated phospho-Rabs in tauopathies and synucleinopathies.Acta neuropathologica · 2025Article
- Lrrk2 G2019S mutation incites increased cell-intrinsic neutrophil effector functions and intestinal inflammation in a model of infectious colitis.NPJ Parkinson's disease · 2025Article
- Comparative Molecular Dynamics Reveals How LRRK2 Inhibitors Distinguish G2019S from Wild-Type.Neurochemical research · 2025Article
- Critical analysis of translational potential of rodent models of white matter pathology across a wide spectrum of human diseases.Cell death & disease · 2025Review
- Oxidative Stress: Pathological Driver in Chronic Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- LRRK2-mediated mitochondrial dysfunction in Parkinson's disease.The Biochemical journal · 2025Review
- Parkinson's Disease: The Neurodegenerative Enigma Under the "Undercurrent" of Endoplasmic Reticulum Stress.International journal of molecular sciences · 2025Review
- Brain organoids: a new paradigm for studying human neuropsychiatric disorders.Frontiers in neuroscience · 2025Review
- Spatiotemporal crosstalk among mitochondrial dynamics, NLRP3 inflammasome activation, and histone lactylation drivesFrontiers in cellular neuroscience · 2025Review
- Studying Rare Movement Disorders: From Whole-Exome Sequencing to New Diagnostic and Therapeutic Approaches in a Modern Genetic Clinic.Biomedicines · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Pathogenic mutations in LRRK2 cause Parkinson's disease (PD). The G2019S variant is the most common, which results in abnormally high kinase activity. Compounds that target LRRK2 kinase activity are currently being developed and tested in clinical trials. We recently found that G2019S LRRK2 causes mitochondrial DNA (mtDNA) damage and treatment with multiple classes of LRRK2 kinase inhibitors at concentrations associated with dephosphorylation of LRRK2 reversed mtDNA damage to healthy control levels. Because maintaining the normal function of LRRK2 in heterozygous G2019S LRRK2 carriers while specifically targeting the G2019S LRRK2 activity could have an advantageous safety profile, we explored the efficacy of a G2019S mutant selective LRRK2 inhibitor to reverse mtDNA damage in G2019S LRRK2 models and patient cells relative to non-selective LRRK2 inhibitors. Potency of LRRK2 kinase inhibition by EB-42168, a G2019S mutant LRRK2 kinase inhibitor, and MLi-2, a non-selective inhibitor, was determined by measuring phosphorylation of LRRK2 at Ser935 and/or Ser1292 using quantitative western immunoblot analysis. The Mito DNA
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.