Fig. 6

Schematic representation of the participation of NFAT on synapse degeneration in synucleinopathies. A specific population of aSyn-O present in the extracellular milieu could be inserted in the plasma membrane leading to leakage of calcium to the interior of the neurons. Upon calcium binding, activation of calcineurin takes place. This phosphatase dephosphorylates the hyperphosphorylated, inactive NFAT leading to its activation and translocation to the nucleus. There, NFAT binds to its cognate promoter sequences including the one that regulates the expression of the gene of synapsin 1 (Syn1). NFAT downregulates the expression of this gene decreasing the amount synapsin 1, a protein that is involved in vesicle trafficking facilitating neurotransmitter release. This cascade of events leads to synapse degeneration one of the events observed in PD and other synucleionopathies