Background: The sterile alpha motif (Sam) domain is a small helical protein module,
able to undergo homo- and hetero-oligomerization, as well as polymerization, thus forming
different types of protein architectures. A few Sam domains are involved in pathological
processes and consequently, they represent valuable targets for the development of new potential
therapeutic routes. This study intends to collect state-of-the-art knowledge on the different
modes by which Sam domains can favor disease onset and progression.
Methods: This review was build up by searching throughout the literature, for: a) the structural
properties of Sam domains, b) interactions mediated by a Sam module, c) presence of a
Sam domain in proteins relevant for a specific disease.
Results: Sam domains appear crucial in many diseases including cancer, renal disorders, cataracts.
Often pathologies are linked to mutations directly positioned in the Sam domains that
alter their stability and/or affect interactions that are crucial for proper protein functions. In
only a few diseases, the Sam motif plays a kind of "side role" and cooperates to the pathological
event by enhancing the action of a different protein domain.
Conclusion: Considering the many roles of the Sam domain into a significant variety of diseases,
more efforts and novel drug discovery campaigns need to be engaged to find out small
molecules and/or peptides targeting Sam domains. Such compounds may represent the pillars
on which to build novel therapeutic strategies to cure different pathologies.