Molecular Mechanisms of LRRK2 in Neuronal Function and Neurodegeneration

Leucine rich repeat kinase 2 (LRRK2) sits at a crossroads of neuronal biology, linking membrane trafficking, lysosomal and autophagic function, mitochondrial health and immune signalling. Mutations in LRRK2 are among the most common genetic causes of familial and sporadic Parkinson's disease, yet the molecular events that connect altered LRRK2 activity to neuronal dysfunction are still only partly understood.This Research Topic focuses on the molecular and cellular mechanisms of LRRK2, from its core enzymatic activity to its wider roles in cell biology and disease. We welcome Original Research, Reviews, Mini Reviews, Methods and Perspectives that deepen mechanistic understanding of LRRK2, using molecular, genetic, cell biological and omics approaches.The themes of interest include, but are not limited to:• Kinase and GTPase activity of LRRK2 and its regulation• Rab GTPase substrates and LRRK2 dependent membrane and vesicle trafficking• Lysosomal, endolysosomal and autophagic function downstream of LRRK2• Mitochondrial and metabolic effects of LRRK2 activity• LRRK2 in neuroinflammation and immune signalling• Convergence of LRRK2 with other genetic risk factors such as GBA, including shared mechanisms and questions of penetrance• LRRK2 associated biomarkers, including BMP, and the relevance of LRRK2 beyond Parkinson's, for example in progressive supranuclear palsy and Alzheimer's disease• Mechanistic insight into LRRK2 pathogenic variants and their cellular consequences• Molecular basis of LRRK2 targeted approaches, including kinase inhibition• Patient derived cells, model organisms and omics approaches to LRRK2 mechanism Topic editors: KaiYin Chau, Tiago F Outeiro Source: https://www.frontiersin.org/research-topics/85038/molecular-mechanisms-of-lrrk2-in-neuronal-function-and-neurodegeneration