Modulating autophagy to treat CV disease

Brought to you by the Fondation Leducq Transatlantic Network of Excellence

Cuervo Lab

Principal Investigator:

Ana Maria Cuervo, MD, PhD

Leducq Lab Members: 

Julio Madrigal-Mature, PhD (Leducq Fellow)
Susmita Kaushik, PhD

Contribution to the network:

The Cuervo lab has a long-standing expertise in the molecular mechanisms of autophagy and the contribution of malfunctioning of this process to age-related disorders, including metabolic diseases. Our group contributes to this network’s expertise of autophagy in general and more specifically on selective forms of autophagy such as lipophagy and chaperone-mediated autophagy (CMA).

The goal of our studies in the network is to understand the role of CMA in the regulation of intracellular lipid metabolism and in the defense against lipotoxicity and to elucidate the contribution of the inhibitory effect of CMA on age and metabolic challenges to atherosclerosis.

Our hypothesis is that sustained metabolic challenges can inhibit CMA function and that conversely, a decline in CMA function can promote chronic metabolic dysfunction in aging, thereby creating a vicious cycle that amplifies the risk for atherosclerosis.

Significance: If our hypothesis is correct, interventions aimed at preventing or reverting the autophagic failure related to aging or excessive lipid diets could have a great therapeutic potential against the CVD. In fact, our group has started the development of chemical compounds that modulate autophagic activity and that we anticipate could be used to prevent the decline of autophagy with age and Western lifestyle and thus delay metabolic diseases such as atherosclerosis.