Inhibition of inositol monophosphatase (IMPase) at the calbindin-D28k binding site: Molecular and behavioral aspects

Suppressed Calbindin Levels in Hippocampal Excitatory Neurons Mediate Stress-Induced Memory Loss

“…Remarkably, the cell adhesion molecule nectin3 colocalizes and interacts with calbindin in hippocampal neurons, indicative of nectin3 as an upstream molecule of calbindin. Moreover, calbindin has been shown to interact with and activate IMPase (Berggard et al, 2002;Levi et al, 2013), a key enzyme in the phosphatidylinositol-signaling pathway. We found that early-life stress lastingly lowered hippocampal IMPase levels, which can be reproduced by knockdown of either nectin3 or calbindin and prevented by CRHR1 blockade.…”

“…Calbindin can activate inositol monophosphatase (IMPase), a key enzyme in the phosphatidylinositol signaling pathway that modulates memory (Berggard et al, 2002;Figueiredo et al, 2016;Levi et al, 2013). We observed that early-life stress reduced IMPase levels in the adult hippocampus, especially in CA1-3 subregions ( Figure S5K), which can be reversed by CRHR1 antagonism ( Figure S5L).…”

Exploring Calbindin-IMPase fusion proteins structure and activity

“…Data were analyzed using the SCÅTTER and ATSAS program suites (Franke et al, 2017; Franke and Svergun, 2009; Kozin and Svergun, 2001). The FoXS web server was employed to compute the theoretical scattering profile using a computational docking model of the calbindin-IMPase interaction [ 17 ] for comparison with the experimental data (Schneidman-Duhovny et al, 2013, 2016).…”

“…Both these residues are involved in calcium coordination. These data were utilised to design peptide inhibitors [ 17 ]. The interest in this interaction is now of burning interest because of the therapeutic potential of IMPase in bipolar disorder.…”

Estudo do hipocampo de portadores de transtorno afetivo bipolar após o primeiro episódio de mania através do uso da espectroscopia por ressonância magnética de próton (1H-ERM)

“…Estudos têm observado que o lítio de fato diminui os níveis de inositol (Moore et al, 1999;Davanzo et al, 2001), porém a inibição da IMP é considerada modesta e não está claro se é suficiente para levar a alterações importantes dessa via. Há também um descompasso entre a mudança biquímica imediata e o efeito clínico mais demorado do lítio, o que também diminui o valor dessa hipótese, que tem sido questionada, apesar de ainda ser uma referência importante na discussão da fisiopatologia do TAB (Levi et al, 2013).…”