LRRK2

Leucine-rich repeat kinase 2 (LRRK2), also known as dardarin, is a large multidomain protein kinase that includes leucine-rich repeats and a GTPase domain. Mutations in LRRK2 are commonly associated with late-onset Parkinson's disease (PD).

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
6071 CZC 25146
Potent LRRK2 inhibitor
4534 CZC 54252 hydrochloride
Potent LRRK2 inhibitor; neuroprotective
4629 GSK2578215A
Potent, selective LRRK2 inhibitor; brain penetrant
6289 JH-II-127
Potent and selective LRRK2 inhibitor
4273 LRRK2-IN-1
Potent and selective LRRK2 inhibitor
5756 MLi-2
Potent and selective LRRK2 inhibitor
5716 PF 06447475
Potent LRRK2 inhibitor; neuroprotective

Related Targets

    Leucine-rich repeat kinase 2 (LRRK2), also known as dardarin, is a large multidomain protein kinase that includes leucine-rich repeats and a GTPase domain. LRRK2 is encoded by the PARK8 gene.

    Autosomal dominant missense mutations in LRRK2 are commonly associated with late-onset Parkinson's disease (PD); they are also evident in a smaller percentage of familial Parkinson's disease cases, of which they are the most common cause. The discovery of LRRK2 mutations helped strengthen a genetic link to Parkinson's disease, which had previously been obscured by unusual inheritance patterns - in particular, incomplete/decreased penetrance and variable age of onset. Mutations associated with PD have been isolated within the enzymatic domains of LRRK2, namely its kinase and GTPase domains. The most frequent mutation is a substitution of the Gly2019 residue in the kinase domain with a serine residue, resulting in a kinase that exhibits 2- to 3-fold greater catalytic activity. Pathogenic mutations within the Roc (Ras of complex) GTPase domain and COR (carboxy-terminal of Roc) sequence have been shown to decrease GTPase activity, which is thought to counteract LRRK2 activity and restore it to basal levels. Inhibitors of LRRK2 kinase activity have therefore been of therapeutic interest in the treatment of LRRK2-linked PD.

    LRRK2 also contains protein-protein interaction domains. Proteins thought to interact with LRRK2 include dishevelled proteins, MAPK kinase 6 (MKK6) and 14.3.3 proteins. Studies have shown that certain members of the 14-3-3 family bind and influence the cytoplasmic localization of LRRK2. PD-associated mutants and a truncated form of LRRK2 show a decreased ability to bind 14-3-3, suggesting that this interaction is important in the pathogenesis of PD.

    Literature for LRRK2

    Kinases

    Kinases Product Listing

    A collection of over 400 products for kinase research, the listing includes inhibitors of:

    • Receptor Tyrosine Kinases
    • Protein Kinases A, C, D and G
    • PI-3 Kinase, Akt and mTOR
    • MAPK Signaling
    • Receptor Serine/Threonine Kinases
    Neurodegeneration

    Neurodegeneration Product Guide

    A collection of over 275 products for neurodegeneration research, the guide includes research tools for the study of:

    • Alzheimer's disease
    • Parkinson's disease
    • Huntington's disease
    Parkinson's

    Parkinson's Poster

    Parkinson's disease (PD) causes chronic disability and is the second most common neurodegenerative condition. This poster outlines the neurobiology of the disease, as well as highlighting current therapeutic treatments for symptomatic PD, and emerging therapeutic strategies to delay PD onset and progression.

    LRRK2 Gene Data

    Gene Species Gene Symbol Gene Accession No. Protein Accession No.
    Leucine-Rich Repeat Kinase 2 Human LRRK2 XM_058513 Q5S007
    Mouse Lrrk2 NM_025730 Q5S006
    Rat Lrrk2 NM_001191789 NP_001178718