Fig. 1

Defects in autophagy associated with LRRK2 mutations. a Mutant LRRK2 induces autophagosome formation by activating the MEK/ERK pathway and the Ca²⁺-dependent AMPK pathway. b Fusion of autophagosome with lysosome is blocked, exacerbating autophagosome accumulation. c Mutant LRRK2 binds to LAMP2A and prevents its multimerization to form the translocation complex required for transport of CMA substrates into lysosome for degradation. d Mutant LRRK2 promotes binding of α-syn onto lysosomal membranes where they form oligomers. e Impaired protein trafficking from endosome to trans-Golgi network due to retromer dysfunction leads to hydrolase deficiencies in lysosome