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Updated: Dec 5, 2025

Assaying the Kinase Activity of LRRK2 in vitro
06:09

Assaying the Kinase Activity of LRRK2 in vitro

Published on: January 18, 2012

22.9K

Allosteric inhibition of LRRK2, where are we now

Ahmed Soliman1, Fatma Nihan Cankara2, Arjan Kortholt1,2

  • 1Department of Cell Biochemistry, University of Groningen, Groningen, The Netherlands.

Biochemical Society Transactions
|October 20, 2020
PubMed

Insights

New Parkinson's disease (PD) therapies focus on allosteric LRRK2 inhibitors. This approach bypasses safety concerns of current ATP-competitive drugs, offering a promising alternative for treating this neurodegenerative disease.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Genetics

Background:

  • Parkinson's disease (PD) is a prevalent neurodegenerative disorder.
  • Leucine-rich repeat kinase 2 (LRRK2) plays a key role in both familial and sporadic PD.
  • Pathogenic LRRK2 mutations increase its kinase activity, making it a therapeutic target.

Purpose of the Study:

  • To review recent advancements in developing allosteric LRRK2 inhibitors.
  • To explore alternative strategies for targeting LRRK2 activity beyond ATP-competitive inhibition.
  • To identify novel intra- and interprotein interaction targets for PD therapeutics.

Main Methods:

  • Review of current literature on LRRK2 inhibitors.
  • Analysis of allosteric inhibition mechanisms, focusing on GTPase activity.
  • Identification of potential new therapeutic targets within LRRK2 pathways.

Main Results:

  • Development of selective LRRK2 inhibitors with brain availability.
  • Concerns regarding the long-term safety of ATP-competitive LRRK2 inhibitors.
  • Emergence of allosteric inhibition as a viable therapeutic strategy.

Conclusions:

  • Allosteric LRRK2 inhibitors offer a safer alternative to ATP-competitive drugs.
  • Targeting LRRK2's GTPase activity is a promising therapeutic avenue.
  • Further research into LRRK2 interactions may unlock new PD treatments.
Keywords:
GTPaseParkinson's diseasedimerizationkinase inhibitorsleucine rich repeat kinase

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