Targeting leucine-rich repeat kinase 2 (LRRK2) for the treatment of Parkinson's disease

• Type: Another Publication in an International Scientific Journal
• Date: 2019

Authors

Domingos, S (Author) Other; Duarte, T (Author) Other; Lucilia Saraiva (Author) FFUP; Guedes, RC (Author) Other; Moreira, R (Author) Other

Journal

Title: Future Medicinal Chemistry

Vol. 11

Pages: 1953-1977

ISSN: 1756-8919

Publisher: Future Medicine Ltd.

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 7 Citations

Other information

Authenticus ID: P-00R-26D

DOI: 10.4155/fmc-2018-0484

Abstract (EN): Leucine-rich repeat kinase 2 (LRRK2) is a serine-threonine kinase involved in multiple cellular processes and signaling pathways. LRRK2 mutations are associated with autosomal-inherited Parkinson's disease (PD), and evidence suggests that LRRK2 pathogenic variants generally increase kinase activity. Therefore, inhibition of LRRK2 kinase function is a promising therapeutic strategy for PD treatment. The search for drug-like molecules capable of reducing LRRK2 kinase activity in PD led to the design of selective LRRK2 inhibitors predicted to be within the CNS drug-like space. This review highlights the journey that translates chemical tools for interrogating the role of LRRK2 in PD into promising drug candidates, addressing the challenges in discovering selective and brain-penetrant LRRK2 modulators and exploring the structure-activity relationship of distinct LRRK2 inhibitors.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 25