Peptides and peptidomimetics: their relevance in autophagy regulation in biomedicine

Autophagy is a cellular process mediating degradation of bulk cytoplasm, long-lived proteins and entire organelles. In this process, double-membrane vesicles, the autophagosomes, wrap around portions of cytosol and transport them to the lysosome for degradation. Several molecules participate in autophagosome nucleation and elongation, including various components of the class III PI3K complex, such as Beclin 1 and Ambra1 (Activating Molecule in Beclin 1-Regulated Autophagy), which has been recently characterized in our laboratory (1, 2). Any genetic or pharmacological alteration in this process impairs the cell survival rate or cell metabolism, thereby affecting tissue homeostasis (3). Many neurodegenerative conditions, for example, can be traced back to defective autophagy and autophagy has also been identified as a crucial process in oncogenesis and cancer progression. Several autophagy-related proteins have tumor suppressor activity (Beclin 1, Atg5, Bif-1, Atg4C, UVRAG) and some autophagy gene mutations can lead to an accumulation of DNA damage and genome instability. Manipulation of autophagy regulation or of expression and/or function of autophagy genes is therefore of the highest importance in biomedicine. For this reason, the development of molecules, which interfere specifically with autophagy signaling or action, could be useful in the treatment of human disorders. We discuss here the strategies used to manipulate autophagy in several pathological conditions, focussing on the use of small peptides or peptidomimetic molecules in this context.