The role of quality control mechanism in the loss of proteostasis in age-dependent neurodegenerative disorders


Project Summary

Protein misfolding, aggregation and deposition are common disease mechanisms in many neurodegenerative diseases including Parkinson's disease (PD) and Alzheimer’s disease (AD). Autophagic-lysosomal pathway failure may present a key step in the pathological cascade that leads to spreading neurodegeneration. This proposal aims to investigate how autophagy is impaired in AD and PD and how protein misfolding leads to mitochondrial and endoplasmic reticulum stress. Recent work has suggested that exercise may be beneficial in preventing/ameliorating symptoms of several neurological disorders. Moreover long term caloric restriction is known to counteract aging and extend lifespan in several organisms from yeasts to mammals. Taking this into account our major goal is to evaluate whether these two strategies counteract AD and PD pathology.

Main Goals

The purpose of this project is to evaluate protein quality control systems in in vivo and in vitro models of aging and neurodegeneration, as well as, in brain samples from patients with Parkinson’s or Alzheimer’s disease. Furthermore, we aim to revert proteostasis loss focusing in physical exercise and caloric restriction as therapeutic strategies.

CNC Team

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