Title:Recent Update on the Development of Leucine-Rich Repeat Kinase 2
(LRRK2) Inhibitors: A Promising Target for the Treatment of Parkinson’s
Disease
Volume: 18
Issue: 7
Author(s): Ashish Patel*, Stuti Patel, Meshwa Mehta, Yug Patel, Dhruv Langaliya, Shyam Bhalodiya and Tushar Bambharoliya
Affiliation:
- Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus,
Changa 388421, Anand, Gujarat, India
Keywords:
Leucine-rich repeat kinase 2 (LRRK2), Parkinson's disease (PD), brain penetrant LRKK2 inhibitors, G2019SLRRK2 mutant, wild-type LRKK2, promising target.
Abstract: Parkinson’s disease is a relatively common neurological disorder with incidence increasing
with age. Since current medications only relieve the symptoms and do not change the course of
the disease, therefore, finding disease-modifying therapies is a critical unmet medical need. However,
significant progress in understanding how genetics underpins Parkinson's disease (PD) has opened
up new opportunities for understanding disease pathogenesis and identifying possible therapeutic
targets. One such target is leucine-rich repeat kinase 2 (LRRK2), an elusive enzyme implicated in
both familial and idiopathic PD risk. As a result, both academia and industry have promoted the development
of potent and selective inhibitors of LRRK2. In this review, we have summarized recent
progress in the discovery and development of LRKK2 inhibitors as well as the bioactivity of several
small-molecule LRRK2 inhibitors that have been used to inhibit LRRK2 kinase activity in vitro or
in vivo.