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PERSPECTIVE article
Front. Cell Dev. Biol.
Sec. Signaling
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1569733
This article is part of the Research TopicNeuronal Guidance Signaling in Health and Neurological DiseasesView all 7 articles
Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects
Provisionally accepted- University of Wisconsin–Milwaukee, Milwaukee, United States
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In humans, variants in the LRRK2 gene are the most prevalent risk factors for Parkinson's disease (PD). Whereas studies in model organisms have long indicated that the orthologs of the wild-type LRRK proteins protect against neurodegeneration, newer findings indicate that they also protect against neurodevelopmental defects. This normal role of the LRRK proteins can be disrupted by either gain-of-function (GOF) or loss-of-function (LOF) mutations, leading to neurodegeneration and neurodevelopmental defects. Here, we review the roles of the LRRK proteins and their orthologs in these processes, with a focus on autophagy as a common factor that may mediate both of these roles. We also highlight the potential for experiments in vertebrate and invertebrate model systems to synergistically inform our understanding of the role of LRRK proteins in protecting against neurological disorders.
Keywords: LRRK 2, Parkinson's disease, autism, Intelectual Disability, Neurodegenaration
Received: 01 Feb 2025; Accepted: 21 Apr 2025.
Copyright: © 2025 Tran Nguyen, Nhat Nguyen, Stokke and Quinn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
An Phu Tran Nguyen, University of Wisconsin–Milwaukee, Milwaukee, United States
Christopher C. Quinn, University of Wisconsin–Milwaukee, Milwaukee, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.