ArticleJournal of Parkinson's disease2021
Combined Knockout of Lrrk2 and Rab29 Does Not Result in Behavioral Abnormalities in vivo.
Article in Journal of Parkinson's disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Aging, Parkinson's Disease, and Models: What Are the Challenges?Aging biology · 2023Article
- Rab GTPases in Parkinson's disease: a primer.Essays in biochemistry · 2021Article
- Increased LRRK2 kinase activity alters neuronal autophagy by disrupting the axonal transport of autophagosomes.Current biology : CB · 2021Article
- Significance of Parkinson Family Genes in the Prognosis and Treatment Outcome Prediction for Lung Adenocarcinoma.Frontiers in molecular biosciences · 2021Article
- Endogenous Rab29 does not impact basal or stimulated LRRK2 pathway activity.The Biochemical journal · 2020Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCoding mutations in the LRRK2 gene, encoding for a large protein kinase, have been shown to cause familial Parkinson's disease (PD). The immediate biological consequence of LRRK2 mutations is to increase kinase activity, suggesting that inhibition of this enzyme might be useful therapeutically to slow disease progression. Genome-wide association studies have identified the chromosomal loci around LRRK2 and one of its proposed substrates, RAB29, as contributors towards the lifetime risk of sporadic PD.
objectiveConsidering the evidence for interactions between LRRK2 and RAB29 on the genetic and protein levels, we set out to determine whether there are any consequences on brain function with aging after deletion of both genes.
methodsWe generated a double knockout mouse model and performed a battery of motor and non-motor behavioral tests. We then investigated postmortem assays to determine the presence of PD-like pathology, including nigral dopamine cell count, astrogliosis, microgliosis, and striatal monoamine content.
resultsBehaviorally, we noted only that 18-24-month Rab29-/- and double (Lrrk2-/-/Rab29-/-) knockout mice had diminished locomotor behavior in open field compared to wildtype mice. However, no genotype differences were seen in the outcomes that represented PD-like pathology.
conclusionThese results suggest that depletion of both LRRK2 and RAB29 is tolerated, at least in mice, and support that this pathway might be able to be safely targeted for therapeutics in humans.
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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.