ReviewExperimental neurology2017
Achieving neuroprotection with LRRK2 kinase inhibitors in Parkinson disease.
Review in Experimental neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
91 citing papers in PubMed, 170 citations in OpenAlex.
- Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson's Disease.Biomedicines · 2026Review
- Leucine-Rich Repeat Kinase 2 (LRRK2) in Glucose Metabolism and Metabolic-Neuroinflammatory Crosstalk.Biomolecules · 2026Review
- LRRK2 kinase activity restricts NRF2-dependent mitochondrial protection in microglia.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- LRRK2 G2019S reprograms innate and adaptive immunity to drive context-dependent host defense outcomes.Frontiers in cellular neuroscience · 2026Article
- LRRK2-mediated mitochondrial dysfunction in Parkinson's disease.The Biochemical journal · 2025Review
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- Genetic mutations in kinases: a comprehensive review on marketed inhibitors and unexplored targets in Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Drug discovery and development for Parkinson's disease: are preclinical models good enough?Frontiers in aging neuroscience · 2025Review
- The design and development of LRRK2 inhibitors as novel therapeutics for Parkinson's disease.Future medicinal chemistry · 2025Review
- LRRK2 in Parkinson's disease: upstream regulation and therapeutic targeting.Trends in molecular medicine · 2024Review
- Molecular dynamic investigation for Roco4 kinase inhibitor as treatment options for parkinsonism.Journal of molecular modeling · 2024Article
- G2019S selective LRRK2 kinase inhibitor abrogates mitochondrial DNA damage.NPJ Parkinson's disease · 2024Article
- Causal relationship between coffee intake and neurological diseases: a Mendelian randomization study.European journal of clinical nutrition · 2024Article
- Pharmacology of LRRK2 with type I and II kinase inhibitors revealed by cryo-EM.Cell discovery · 2024Article
- Knockdown of LRRK2 inhibits the progression of lung cancer by regulating TLR4/NF-κB pathways and NLRP3 inflammasome.Journal of clinical biochemistry and nutrition · 2023Article
- Genetic Testing forMovement disorders clinical practice · 2023Article
- A leucine-rich repeat kinase 2 (LRRK2) pathway biomarker characterization study in patients with Parkinson's disease with and without LRRK2 mutations and healthy controls.Clinical and translational science · 2023Article
- The Rare Marine Bioactive Compounds in Neurological Disorders and Diseases: Is the Blood-Brain Barrier an Obstacle or a Target?Marine drugs · 2023Review
- Parkinson's Disease: Exploring Different Animal Model Systems.International journal of molecular sciences · 2023Review
- Capturing Differences in the Regulation of LRRK2 Dynamics and Conformational States by Small Molecule Kinase Inhibitors.ACS chemical biology · 2023Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
In the translation of discoveries from the laboratory to the clinic, the track record in developing disease-modifying therapies in neurodegenerative disease is poor. A carefully designed development pipeline built from discoveries in both pre-clinical models and patient populations is necessary to optimize the chances for success. Genetic variation in the leucine-rich repeat kinase two gene (LRRK2) is linked to Parkinson disease (PD) susceptibility. Pathogenic mutations, particularly those in the LRRK2 GTPase (Roc) and COR domains, increase LRRK2 kinase activities in cells and tissues. In some PD models, small molecule LRRK2 kinase inhibitors that block these activities also provide neuroprotection. Herein, the genetic and biochemical evidence that supports the involvement of LRRK2 kinase activity in PD susceptibility is reviewed. Issues related to the definition of a therapeutic window for LRRK2 inhibition and the safety of chronic dosing are discussed. Finally, recommendations are given for a biomarker-guided initial entry of LRRK2 kinase inhibitors in PD patients. Four key areas must be considered for achieving neuroprotection with LRRK2 kinase inhibitors in PD: 1) identification of patient populations most likely to benefit from LRRK2 kinase inhibitors, 2) prioritization of superior LRRK2 small molecule inhibitors based on open disclosures of drug performance, 3) incorporation of biomarkers and empirical measures of LRRK2 kinase inhibition in clinical trials, and 4) utilization of appropriate efficacy measures guided in part by rigorous pre-clinical modeling. Meticulous and rational development decisions can potentially prevent incredibly costly errors and provide the best chances for LRRK2 inhibitors to slow the progression of PD.
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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.