Proteases at work: Cues for understanding neural development and degeneration

Proteolytical processing of membrane bound molecules is a fundamental mechanism for the degradation of these proteins as well as for controlling cell-to-cell communication, which is at the basis of tissue development and homeostasis. Members of families of metalloproteinases and intra-membrane proteases are major effectors of these events. A recent workshop in Baeza, Spain, was devoted to discuss how this mechanism coordinates brain development and how its dysfunction leads to brain pathologies. Herein we summarize the findings presented during this workshop, which illuminate the role of metalloproteinases, including matrix metalloproteinase, A Disintegrin and Metalloproteinase-proteases and intra-membrane proteases, in the regulation of neurogenesis, axon guidance, and synaptogenesis as well as in neurodegeneration. Indeed, there is increasing evidence that proteolysis at the membrane is directly linked to neuropathologies such as Alzheimer Disease and autism spectrum or prion disorders. These proteolytic events are tightly regulated and we are just at the beginning of understanding how these processes could be exploited to design therapeutic treatments aimed at alleviating psychiatric and neurodegenerative pathologies.Work in PB lab is supported by grants from the Spanish MINECO (BFU2010-16031; BFU2013-43213), Comunidad Autonoma de Madrid (CAM, S2010/BMD-2315) Cost Action BM1001 “Brain ECM in Health and Disease”, Fundación Tatiana Pérez de Guzmán el Bueno and CIBERER and an institutional grant from the Fundación Ramon Areces. Work in PS lab is supported by the Deutsche Forschungsgemeinschaft (DFG), SFB877 A3 and A12 and Interuniversity Attraction Poles ProgramIUAP P7/16 of the Belgian Federal Science Policy OfficePeer Reviewe