STRATEGIES D'IDENTIFICATION DES SECRETASES IMPLIQUEES DANS LA MALADIE D'ALZHEIMER

In Alzheimer's disease, cortical areas of affected patients are invaded by extracellular proteinous deposits called senile plaques, the main component of which is called amploid β-peptide or Aβ. This peptide derives from the proteolytic attack of a precursor, the β-amyloid precursor protein, by two enzymes called β- and γ-secretases. Alternatively, βAPP can be cleaved by an additional activity named α-secretase that occurs inside the Aβ sequence, thereby precluding its formation, and concomitantly liberating a secreted fragment, namely APPα. Therefore, secretases seem to play a key role in the control of physiological and potentially pathogenic βAPP catabolites and could be envisioned as possible therapeutic targets in Alzheimers disease. Here, we describe possible experimental approaches to identify such proteolytic activities.