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- W2946804521 endingPage "130" @default.
- W2946804521 startingPage "121" @default.
- W2946804521 abstract "Several kinases have been implicated in the pathogenesis of Parkinson's disease (PD), most notably leucine-rich repeat kinase 2 (LRRK2), as LRRK2 mutations are the most common genetic cause of a late-onset parkinsonism that is clinically indistinguishable from sporadic PD. More recently, several other kinases have emerged as promising disease-modifying targets in PD based on both preclinical studies and clinical reports on exenatide, the urate precursor inosine, nilotinib and lithium use in PD patients. These kinases include protein kinase B (Akt), glycogen synthase kinases-3β and -3α (GSK-3β and GSK-3α), c-Abelson kinase (c-Abl) and cyclin-dependent kinase 5 (cdk5). Activities of each of these kinases are involved either directly or indirectly in phosphorylating tau or increasing α-synuclein levels, intracellular proteins whose toxic oligomeric forms are strongly implicated in the pathogenesis of PD. GSK-3β, GSK-3α and cdk5 are the principle kinases involved in phosphorylating tau at sites critical for the formation of tau oligomers. Exenatide analogues, urate, nilotinib and lithium have been shown to affect one or more of the above kinases, actions that can decrease the formation and increase the clearance of intraneuronal phosphorylated tau and α-synuclein. Here we review the current preclinical and clinical evidence supporting kinase-targeting agents as potential disease-modifying therapies for PD patients enriched with these therapeutic targets and incorporate LRRK2 physiology into this novel model." @default.
- W2946804521 created "2019-05-29" @default.
- W2946804521 creator A5038069496 @default.
- W2946804521 creator A5052009114 @default.
- W2946804521 creator A5061861586 @default.
- W2946804521 creator A5085303733 @default.
- W2946804521 date "2019-07-01" @default.
- W2946804521 modified "2023-10-01" @default.
- W2946804521 title "Targeting kinases in Parkinson's disease: A mechanism shared by LRRK2, neurotrophins, exenatide, urate, nilotinib and lithium" @default.
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