Contribution of Aging of Selective Autophagy to Neurodegeneration

Identification: Cuervo, Ana Maria


Description

Contribution of Aging of Selective Autophagy to Neurodegeneration
 
Ana Maria Cuervo, MD PhD
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA
 
Cells count on surveillance systems to handle protein alterations and organelle damage. Malfunctioning of these systems contribute in large extend to the abnormal accumulation of those altered components in cells and tissues in numerous diseases and in aging. Our recent studies have focused primarily on the degradation of proteins in lysosomes through a selective form of autophagy, known as chaperone-mediated autophagy (CMA).
Cytosolic proteins substrate for CMA are delivered to the lysosomal lumen for degradation by directly crossing the lysosomal membrane. This process is mediated by a set of cytosolic and lysosomal chaperones and by a receptor protein at the lysosomal membrane, the lysosome-associated membrane protein type 2A (LAMP-2A). The limiting step of this type of autophagy is the binding of substrates to LAMP-2A and the organization of this protein as a translocation complex at he lysosomal membrane. We have learnt that the process of assembly and disassembly of LAMP-2A is a vulnerable step of CMA in pathological conditions and in aging.
In recent years, the better molecular characterization of CMA and the development by our group of mouse models with selective blockage of CMA has considerably advanced our understanding of the physiological role of this pathway in neuronal pathophysiology. In this talk, I will describe our recent findings on the consequences of the functional decline of CMA with age on brain aging and on the progression of different neurodegenerative disorders. I will also share some of our current efforts to modulate CMA activity either genetically or chemically with neuroprotective purposes in aging.
 
This work is supported by NIH grants: AG021904, AG031782, AG054108, NS100717 and the Rainwaters Foundation.
 

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