Leucine-rich repeat kinase 2 (LRRK2) inhibitors for Parkinson's disease: a patent review of the literature to date

被引:2
|
作者
Morez, Margaux [1 ]
Ordonez, Antonio Jesus Lara [1 ]
Melnyk, Patricia [1 ]
Liberelle, Maxime [1 ]
Lebegue, Nicolas [1 ]
Taymans, Jean-Marc [1 ]
机构
[1] Univ Lille, U1172, LilNCog, Lille Neurosci & Cognit,INSERM,CHU Lille, Lille, France
关键词
LRRK2; kinase; allosteric; GTPase; Parkinson's disease; conformation; ALPHA-SYNUCLEIN; 14-3-3; BINDING; MUTATIONS; G2019S; PHOSPHORYLATION; IDENTIFICATION; DOMAIN; LUNG; ROC;
D O I
10.1080/13543776.2024.2378076
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
IntroductionNearly two decades after leucine rich repeat kinase 2 (LRRK2) was discovered as a genetic determinant of Parkinson's disease (PD), LRRK2 has emerged a priority therapeutic target in PD and inhibition of its activity is hypothesized to be beneficial.Areas coveredLRRK2 targeting agents, in particular kinase inhibitors and agents reducing LRRK2 expression show promise in model systems and have progressed to phase I and phase II clinical testing for PD. Several additional targeting strategies for LRRK2 are emerging, based on promoting specific 'healthy' LRRK2 quaternary structures, heteromeric complexes and conformations.Expert opinionIt can be expected that LRRK2 targeting strategies may proceed to phase III clinical testing for PD in the next five years, allowing the field to discover the real clinical value of LRRK2 targeting strategies.
引用
收藏
页码:773 / 788
页数:16
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