In:
Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 15, No. 748 ( 2022-08-23)
Abstract:
Activating mutations in the kinase LRRK2 cause Parkinson’s disease (PD) in some patients. Mutant LRRK2 can promote the processing of APP into its transcriptionally active form, the APP intracellular domain (AICD). Zhang et al. showed that these proteins are linked in a self-perpetuating cycle. In cultured neurons and brain tissue from mouse models of PD, LRRK2-mediated phosphorylation of APP increased the abundance and activity of the AICD that then directly mediated LRRK2 transcription. Pathological markers in LRRK2-mutant PD models were reduced by targeting the AICD with itanapraced, a small-molecule inhibitor that is currently in trials to treat Alzheimer’s disease. The findings reveal that LRRK2 and the AICD are reciprocally linked and that itanapraced may be therapeutically beneficial in PD.
Type of Medium:
Online Resource
ISSN:
1945-0877
,
1937-9145
DOI:
10.1126/scisignal.abk3411
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2022
