TrkB and the calpain dependent-Tc TrkB receptor isoforms: possibleneurological therapeutic targets

DANIEL MASCÒ; CRAGNOLINI,ANDRREA; DANELON, VICTOR

Journal of Neurology and Neuromedicine

SCIACCESS PUBLISHERS

Año: 2016 vol. 1 p. 31 - 36

2572-942X

Several neurological conditons share a characteristc feature: an increasein intracellular calcium levels ([Ca2+]i). It has been demonstrated that calciuminflux induces changes ranging from an increase in the expression levels ofseveral genes to the actvaton of proteases such as calpains. Calpains are afamily of Ca2+-dependent non-lysosomal cysteine proteases, whose substratesinclude several proteins that play critcal roles in several cellular functonsincluding synaptc plastcity and neuronal apoptosis.TrkB is a type of tyrosine related kinase receptor that can promoteneuronal survival and differentaton upon ligand binding. It has been recentlyshown that in several neurological diseases, the level of full-length TrkB protein decreases before the onset of neuronal death due to one of two differentprocesses: a) a reverse regulaton of TrkB isoforms mRNA, or b) calpainmediated processing of TrkB full-length, which yields a truncated form of TrkB(Tc-TrkB). Because the most notorious feature of calpain proteolytc actvity isthat the products of calpain-mediated cleavage may have biological actvity,here we review the hypotheses by which calpain-generated isoform Tc-TrkBmay perform biological functon