biostudies-literatureUnknown11(1)Pang SYThe Henry G. Leong Endowed Professorship in NeurologyTai Hung Fai Charitable Foundation - Edwin S H Leong Research Programme for Parkinson’s DiseaseThe Donation Fund for Neurology ResearchMutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) represent two most common genetic causes of Parkinson's disease (PD). Both genes are important in the autophagic-lysosomal pathway (ALP), defects of which are associated with α-synuclein (α-syn) accumulation. LRRK2 regulates macroautophagy via activation of the mitogen activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) kinase (MEK) and the calcium-dependent adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathways. Phosphorylation of Rab GTPases by LRRK2 regulates lysosomal homeostasis and endosomal trafficking. Mutant LRRK2 impairs chaperone-mediated autophagy, resulting in α-syn binding and oligomerization on lysosomal membranes. Mutations in GBA reduce glucocerebrosTranslational neurodegeneration5https://www.ebi.ac.uk/biostudies/studies/S-EPMC8805403biostudies-literatureLRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson's disease.PMC8805403Ramsden DBWong WYMalki YChoi ZYChang EESHo PWPang SYLiu HFHo SLLo RCNLeung CTKung MHfalseLRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson's disease.Mutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) represent two most common genetic causes of Parkinson's disease (PD). Both genes are important in the autophagic-lysosomal pathway (ALP), defects of which are associated with α-synuclein (α-syn) accumulation. LRRK2 regulates macroautophagy via activation of the mitogen activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) kinase (MEK) and the calcium-dependent adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathways. Phosphorylation of Rab GTPases by LRRK2 regulates lysosomal homeostasis and endosomal trafficking. Mutant LRRK2 impairs chaperone-mediated autophagy, resulting in α-syn binding and oligomerization on lysosomal membranes. Mutations in GBA reduce glucocerebros2022-01-01T00:00:00Z2022 Jan2025-04-19T10:50:05.266Z2025-04-19T10:50:05.266ZS-EPMC88054033510113410.1186/s40035-022-00281-6