The main focus of our laboratory is to understand how cytosolic proteins are transported into lysosomes for their degradation (autophagy) and how impaired autophagy contributes to aging and age-related diseases.
Autophagy in Neurodegeneration
We have previously identified that multiple pathogenic proteins related with Parkinson’s disease (PD) and Alzheimer’s disease (AD) exert a toxic effect on autophagic pathways including CMA and eMI. We have now confirmed this toxicity in vivo using a novel fluorescent CMA reporter mouse model crossed with a model of PD. Our current efforts focus on identifying the consequences of that toxicity and whether it can be prevented. We have found that reduced CMA accelerates disease progression and propagation in mouse models of frontotemporal dementia and are currently using genetic and chemical approaches in both PD and AD models to determine if activation of CMA could slow disease progression.
Lab website: https://sites.google.com/view/cuervo-lab/