Discovered a small molecule which regenerates neural connections

A team led by Ruth Pérez, a tenured scientist at the Center for Biological Research of the CSIC, has discovered a small molecule capable of promoting the interaction between two proteins that regulates the number and function of synapses.

The scientists, who publish their results in Nature Communications, have used a novel methodology based on a protein-directed dynamic chemical systems. The animal tests carried out in Drosophila models with Alzheimer confirm the regeneration of synapses, the connections between neurons through which the information flows.

The small molecule discovered promotes the interaction between two proteins: the neuronal calcium sensor (NCS-1) and the guanine exchange factor (Ric8a). Both regulate the number and function of synapses, which makes this research a first step for the potential treatment of diseases such as Alzheimer's, Huntington's or Parkinson's, which are characterized by a decrease in the number and efficiency of synapses that precedes neuronal death.

In this paper, a new effective and novel approach in the area of drug discovery that introduces the protein into a dynamic chemical system with an amazing capacity for adaptation is reported. These chemical systems work as in Darwin's Theory of Evolution, where only the fittest molecules are synthesised and survive. In this way, the identification of molecules with affinity for the target protein is directly observed.

This multidisciplinary work has had the outstanding participation of groups of the Structural and Chemical Biology Department of the CIB (NMR, Computation and Translational Medicinal Chemistry). Other collaborators such as the IQFR-CSIC, the UCM, the CiC bioGUNE and the IRyCIS have contributed as well with their studies to this paper.

Reference: Insights into Real-Time Chemical Processes in a Calcium Sensor Protein-Directed Dynamic Library. Andrea Canal-Martín, Javier Sastre, María José Sanchez-Barrena, Angeles Canales, Sara Baldominos, Naiara Pascual, Loreto Martínez-González, Dolores Molero, Mª Encarnación Fernández-Valle, Elena Sáez, Patricia Blanco-Gabella, Elena Gómez-Rubio, Sonsoles Martín-Santamaría, Almudena Sáiz, Alicia Mansilla, F. Javier Cañada, Jesús Jiménez-Barbero, Ana Martínez, Ruth Pérez-Fernández.  Nature Communications. DOI: 10.1038/s41467-019-10627-w

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