ReviewBiochimica et biophysica acta2014
ERKed by LRRK2: a cell biological perspective on hereditary and sporadic Parkinson's disease.
Review in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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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
21 citing papers in PubMed, 37 citations in OpenAlex.
- Environmental Factors Exacerbate Parkinsonian Phenotypes in an Asian-Specific Knock-In LRRK2 Risk Variant in Mice.International journal of molecular sciences · 2025Article
- Precision Medicine in Neurodegenerative Diseases: Genomic Approaches to Target Amyloid-β, Tau, and Alpha-Synuclein Pathways.Current genomics · 2025Review
- Multi-method computational evaluation of the inhibitors against leucine-rich repeat kinase 2 G2019S mutant for Parkinson's disease.Molecular diversity · 2024Article
- Leucine-rich repeat kinase 2 limits dopamine D1 receptor signaling in striatum and biases against heavy persistent alcohol drinking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Recent Advances in the Roles of MicroRNA and MicroRNA-Based Diagnosis in Neurodegenerative Diseases.Biosensors · 2022Review
- MicroRNAs in the pathophysiology of Alzheimer's disease and Parkinson's disease: an overview.Molecular neurobiology · 2022Review
- Molecular mechanisms of developmental pathways in neurological disorders: a pharmacological and therapeutic review.Open biology · 2022Review
- Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration.Translational neurodegeneration · 2022Review
- A Conserved Role for LRRK2 and Roco Proteins in the Regulation of Mitochondrial Activity.Frontiers in cell and developmental biology · 2021Article
- A dual inhibitor targeting HMG-CoA reductase and histone deacetylase mitigates neurite degeneration inAging · 2020Article
- Accelerated telomere shortening independent of LRRK2 variants in Chinese patients with Parkinson's disease.Aging · 2020Article
- MAP/ERK Signaling in Developing Cognitive and Emotional Function and Its Effect on Pathological and Neurodegenerative Processes.International journal of molecular sciences · 2020Review
- Shared (epi)genomic background connecting neurodegenerative diseases and type 2 diabetes.World journal of diabetes · 2020Review
- Mitochondrial Protection by PARP Inhibition.International journal of molecular sciences · 2020Review
- The Drosophila hep pathway mediates Lrrk2-induced neurodegeneration.Biochemistry and cell biology = Biochimie et biologie cellulaire · 2018Article
- LRRK2 Contributes to Secondary Brain Injury Through a p38/Drosha Signaling Pathway After Traumatic Brain Injury in Rats.Frontiers in cellular neuroscience · 2018Article
- TRPM2 Promotes Neurotoxin MPPMolecular neurobiology · 2018Article
- Excitatory Dendritic Mitochondrial Calcium Toxicity: Implications for Parkinson's and Other Neurodegenerative Diseases.Frontiers in neuroscience · 2018Review
- Fibroblast Biomarkers of Sporadic Parkinson's Disease and LRRK2 Kinase Inhibition.Molecular neurobiology · 2016Article
- Non-dopamine receptor ligands for the treatment of Parkinson's disease. Insight into the related chemical/property space.Molecular diversity · 2016Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The leucine rich repeat kinase 2 (LRRK2/dardarin) is implicated in autosomal dominant familial and sporadic Parkinson's disease (PD); mutations in LRRK2 account for up to 40% of PD cases in some populations. LRRK2 is a large protein with a kinase domain, a GTPase domain, and multiple potential protein interaction domains. As such, delineating the functional pathways for LRRK2 and mechanisms by which PD-linked variants contribute to age-related neurodegeneration could result in pharmaceutically tractable therapies. A growing number of recent studies implicate dysregulation of mitogen activated protein kinases 3 and 1 (also known as ERK1/2) as possible downstream mediators of mutant LRRK2 effects. As these master regulators of growth, differentiation, neuronal plasticity and cell survival have also been implicated in other PD models, a set of common cell biological pathways may contribute to neuronal susceptibility in PD. Here, we review the literature on several major cellular pathways impacted by LRRK2 mutations--autophagy, microtubule/cytoskeletal dynamics, and protein synthesis--in context of potential signaling crosstalk involving the ERK1/2 and Wnt signaling pathways. Emerging implications for calcium homeostasis, mitochondrial biology and synaptic dysregulation are discussed in relation to LRRK2 interactions with other PD gene products. It has been shown that substantia nigra neurons in human PD and Lewy body dementia patients exhibit cytoplasmic accumulations of ERK1/2 in mitochondria, autophagosomes and bundles of intracellular fibrils. Both experimental and human tissue data implicate pathogenic changes in ERK1/2 signaling in sporadic, toxin-based and mutant LRRK2 settings, suggesting engagement of common cell biological pathways by divergent PD etiologies.
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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.