The clearance of misfolded proteins in neurodegenerative diseases by zinc metalloproteases: an inorganic perspective

In recent years there has been a wide interest toward zinc metalloproteases involved in neurodegenerative diseases. Enzymes such as matrix metalloproteases, neprilysin, insulin degrading enzyme, etc. play a pivotal role in the homeostasis of peptides and proteins whose accumulation and fibrillation seem to be the major cause for the development of such diseases. It is also well known that chemical factors such as oxidative stress, small molecules and metal ions are able to significantly affect the activity of the above mentioned metalloproteases and therefore, very recently, many research groups have been focused on studying the interaction between those chemical factors and some of the enzymes involved in neurodegenerative diseases. Particularly, metal ions can play various roles (catalytic, structural, allosteric) in enzymes and both the coordination environment as well as the specific metal ion involved, determine the particular function of a metalloprotease. In this article, chemical factors which modulate the activity of zinc metalloproteases involved in neurodegenerative diseases are examined together with recently proposed therapeutic routes related to them. Moreover, two of the most used experimental techniques applied for studying such modulation are also reviewed.