Setting the stage for a role of the postsynaptic proteome in inherited neurometabolic disorders

Abstract

Altres ajuts: Financial support was from Spanish grants ref. BFU2012-34398, BFU2015-69717-P (partially funded by FEDER funds of the EU), Ramón y Cajal Fellowship, ref. RYC-2011-08391 and from the European FP People: Marie Curie Action: Career Integration Grant, ref. 304111. Support was also obtained from the CERCA Programme/Generalitat de Catalunya.

Neurotransmitter diseases are a well-defined group of metabolic conditions caused, in most instances, by genes specifically expressed in the presynaptic button. Better understanding of presynaptic molecular physiology, both in normal and pathological conditions, should help develop therapeutical strategies. The clinical relevance of the presynapse in inherited metabolic disorders is in glaring contrast with that of the postsynaptic component, which so far does not seem to play a relevant role in these disorders. This is somewhat surprising, as postsynaptic proteins are known to be involved in many nervous system diseases, particularly in neurodevelopmental and psychiatric disorders. The goal of this article is to explore if defects in the sophisticated postsynaptic machinery could also have a role in neurometabolic disorders.