The interplay between HPCAL4 and MeCP2: identification and characterization of a novel putative target for Rett syndrome therapy
- 2.3 Years 2022/2024
- 244.999€ Total Award
This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2021
Calcium plays a pivotal role in all cells, especially in neurons where its concentration and dynamics must be tightly regulated to ensure proper functions. Disrupted calcium homeostasis affects neuronal communication which represents a major hallmark of several brain disorders.
In neurons, a poorly studied protein called HPCAL4 seems to be involved in the modulation of calcium dynamics even though its precise role is still unknown. The questions we want to give an answer here are: what is the role of this calcium sensor in healthy neurons during development and in adult life? And then: Is the amount of this protein in neurons, or its functions (or both), playing a role in the development of neurological disabilities in children as in young patients with Rett syndrome?
Why do we think that this sensor is involved in the development of Rett syndrome? Well, we found that brains and neurons affected by Rett syndrome have reduced amount of messenger RNA encoding for this calcium sensor compared to healthy brains and neurons. This association suggests a possible causal correlation between the two conditions. As our observations are also confirmed by other scientists pointing in the same direction, this prompt us to investigate in more details the role of this calcium sensor and its contribution to neuronal function and communication in physiological and pathological contexts. If our experiments will prove that, indeed, this calcium sensor plays a role in the appearance of this neurodevelopmental disorder, then, by studying the mechanisms of action of this protein in healthy neurons and seeing what is wrong in unhealthy ones, we might open new avenues for the development of promising drugs whose activity will have an impact on the severity of Rett symptoms in children, and possibly on other neurological disorders.
