ArticleMolecular neurobiology2015
The Upshot of LRRK2 Inhibition to Parkinson's Disease Paradigm.
Article in Molecular neurobiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Leucine-rich repeat kinase 2 (LRRK2): balancing cellular homeostasis and Parkinson's disease (PD) pathogenesis.Annals of medicine · 2026Review
- 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
- Microtubule acetylation dyshomeostasis in Parkinson's disease.Translational neurodegeneration · 2023Review
- LRRK2 Inhibition by PF06447475 Antagonist Modulates Early Neuronal Damage after Spinal Cord Trauma.Antioxidants (Basel, Switzerland) · 2022Article
- Significant modulations of linc001128 and linc0938 with miR-24-3p and miR-30c-5p in Parkinson disease.Scientific reports · 2022Article
- Defective PTEN-induced kinase 1/Parkin mediated mitophagy and neurodegenerative diseases.Frontiers in cellular neuroscience · 2022Review
- Article
- LRRK2 and mitochondria: Recent advances and current views.Brain research · 2019Review
- Exhaustion of mitochondrial and autophagic reserve may contribute to the development of LRRK2Journal of translational medicine · 2018Observational
- LRRK2 Kinase Activity Induces Mitochondrial Fission in Microglia via Drp1 and Modulates Neuroinflammation.Experimental neurobiology · 2018Article
- Mitochondrial Metabolism Regulates Microtubule Acetylome and Autophagy Trough Sirtuin-2: Impact for Parkinson's Disease.Molecular neurobiology · 2018Article
- Mitochondrial Quality Control in Neurodegenerative Diseases: Focus on Parkinson's Disease and Huntington's Disease.Frontiers in neuroscience · 2018Review
- Mitochondrial Metabolism Power SIRT2-Dependent Deficient Traffic Causing Alzheimer's-Disease Related Pathology.Molecular neurobiology · 2017Article
- Effects of LRRK2 Inhibitors on Nigrostriatal Dopaminergic Neurotransmission.CNS neuroscience & therapeutics · 2017Article
- Back to the tubule: microtubule dynamics in Parkinson's disease.Cellular and molecular life sciences : CMLS · 2017Review
- Mitochondria: A Common Target for Genetic Mutations and Environmental Toxicants in Parkinson's Disease.Frontiers in genetics · 2017Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in leucine-rich repeat kinase 2 gene (LRRK2) are implicated in autosomal dominant familial and sporadic Parkinson's disease (sPD). Given its relative frequency in PD and its putative function in several cellular pathways that are known to be impaired in the disease, we wanted to tackle LRRK2 physiological role and to address its potential as a PD therapeutic target. We investigated the impact of pharmacological inhibition of LRRK2 kinase activity in control and PD cell function. We provide evidence that physiologically LRRK2, through its kinase activity, regulates mitochondrial fission events and facilitates autophagic degradation by modulating lysosomal cellular localization. Upon LRRK2 inhibition, normal fission decreases, leading to the elongation of mitochondrial network which contributes to a poor degradation of deficient mitochondria. Moreover, LRRK2 inhibition promotes lysosomal perinuclear clustering, through Rab7 that further hinders autophagosomes degradation. These events induce a decrease in the autophagic flow, which contributed directly to a decreased proteolytic degradation of damaged mitochondria. These data resembled the results observed in sPD cells. Interestingly, the LRRK2 kinase activity is increased in sPD cells, and despite its inhibition recovers mitochondrial cellular localization, it did not improve microtubule network-dependent trafficking. Our results provide novel insights into the multiple mechanisms that dictate the association between LRRK2 and mitophagy in sPD, and contribute with new findings that could have important therapeutic implications.
Indexed as
Identifiers
What OpenQuestion holds
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.