Our team result of the fusion of the two previous groups of Bertrand Friguet and Mustapha Rouis to create a new team titled: “Integrative cellular ageing and inflammation” for the
Our main goals are to elucidate the role of oxidative and related modifications of proteins as well as the implication of protein maintenance (e.g. oxidized
protein degradation and repair systems) in cellular ageing and in situations of oxidative stress with relevant human cellular models and to investigate the role of the ubiquitous anti-oxidant, anti-inflammatory and anti-apoptotic protein thioredoxin-1 (Trx-1) in arterial protection against oxidative stress and of its truncated pro-inflammatory form (Trx-80) in vascular cellular senescence and inflammation with human macrophages and transgenic mice overexpressing Trx-1 or Trx-80. Extensive investigation on the role of inflammasome NLRP3 in vascular diseases is also conducted.
Cellular ageing has been associated with an increased production of reactive oxygen species also referred as “oxidative stress” and the impairment of cellular defenses against oxidantmediated insults while inflammation, which is also promoting “oxidative stress”, has been recognized as a key component of ageing, also referred as “inflamm’ageing”, at the tissue and organ levels. Hence, cellular senescence, oxidative stress and inflammation are playing a critical role in normal ageing and in the progression of several age-related pathologies for humans, among which cardiovascular diseases that represent one of the main causes of death
in western countries.
Our research proposal is expected to bring fundamental knowledge on protein oxidative modifications and their role in ageing and in the progression of age-related diseases as well as to further develop new approaches for monitoring protein modification at the proteome level. It is also aimed at elucidating the role of Trx-1 in protection against cardiovascular disease-associated oxidative stress especially in pathological vessels remodeling during atherosclerosis and to translate these findings into new therapies based on
Moreover, we study the role of inflammasome NLRP3 in vascular diseases as well as identified specific inhibitors to better control inflammasome NLRP3 activity, in
particular, and inflammation in general. The long term prospect is to define new therapeutic targets within these age-associated pathologies and possibly design and patent selective molecules.