{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lubben N"],"funding":["NIA NIH HHS","Alfred P. Sloan Foundation","Aligning Science Across Parkinson’s","John D. and Catherine T. MacArthur Foundation","Paul G. Allen Family Foundation","National Institute on Aging","Michael J. Fox Foundation for Parkinson&apos;s Research","National Science Foundation"],"pagination":["13"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10910783"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["<h4>Background</h4>Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). These mutations elevate the LRRK2 kinase activity, making LRRK2 kinase inhibitors an attractive therapeutic. LRRK2 kinase activity has been consistently linked to specific cell signaling pathways, mostly related to organelle trafficking and homeostasis, but its relationship to PD pathogenesis has been more difficult to define. LRRK2-PD patients consistently present with loss of dopaminergic neurons in the substantia nigra but show variable development of Lewy body or tau tangle pathology. Animal models carrying LRRK2 mutations do not develop robust PD-related phenotypes spontaneously, hampering the assessment of the efficacy of LRRK2 inhibitors against diseas"],"journal":["Translational neurodegeneration"],"pubmed_title":["LRRK2 kinase inhibition reverses G2019S mutation-dependent effects on tau pathology progression."],"pmcid":["PMC10910783"],"funding_grant_id":["R01 AG077573","PHY-1554488","BCS-1631550","R01 AG076434","16879","ASAP-020616","R01-AG077573"],"pubmed_authors":["Lubben N","Madaj Z","Brynildsen JK","Bassett DS","DeWeerd D","Meymand ES","Fell MJ","Webb CM","O'Reilly M","Li HL","Leyns CEG","Changolkar L","Lee VMY","Zhang B","Henderson MX"],"additional_accession":[]},"is_claimable":false,"name":"LRRK2 kinase inhibition reverses G2019S mutation-dependent effects on tau pathology progression.","description":"<h4>Background</h4>Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). These mutations elevate the LRRK2 kinase activity, making LRRK2 kinase inhibitors an attractive therapeutic. LRRK2 kinase activity has been consistently linked to specific cell signaling pathways, mostly related to organelle trafficking and homeostasis, but its relationship to PD pathogenesis has been more difficult to define. LRRK2-PD patients consistently present with loss of dopaminergic neurons in the substantia nigra but show variable development of Lewy body or tau tangle pathology. Animal models carrying LRRK2 mutations do not develop robust PD-related phenotypes spontaneously, hampering the assessment of the efficacy of LRRK2 inhibitors against diseas","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-16T04:50:07.323Z","creation":"2026-06-16T03:06:42.009Z"},"accession":"S-EPMC10910783","cross_references":{"pubmed":["38438877"],"doi":["10.1186/s40035-024-00403-2"]}}