Structural Biology for Neurodegenerative Diseases
In all living organisms, proteins are the machineries that carry out all the biological processes inside and outside the cells. The understanding of their structure is an important step in figuring out how they work and why an alteration in their structure, and in turn their function, results in disease. Indeed, the protein functions are strictly related to their structures even when proteins are without a defined three-dimensional structure, as in the case of intrinsically disorder proteins. But how do scientists unravel the structures of such macromolecules?
Structural biology is the answer. Structural biology is a branch of biochemistry that studies the structure of macromolecules, such as proteins and nucleic acids. Using and integrating different techniques, structural biology allows the determination of the atomic-detail structure of molecules that otherwise would not be visible. The most commonly used methods are X‐ray crystallography, nuclear magnetic resonance (NMR), and cryo‐electron microscopy (EM). Structural studies can impact on our understanding of neurodegenerative diseases. Amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease among others, are characterised by the gradual loss of neuronal function due to protein aggregation and/or dysfunction. Clarifying the pathophysiological mechanisms behind these diseases is the first step towards the development of effective drugs that can prevent or treat such diseases.
Structural biology in the EuroNeurotrophin Network
Within the “EuroNeurotrophin” network, we aim to crystallise and determine the structures of neurotrophin receptors in complex with small molecules by X-ray crystallography, in order to drive the optimization of lead compounds. Also, we want to integrate this structural information with functional studies by biophysical methods.
About the Author
ESR5: Federica Carucci
Federica is hosted at the University of Siena. Her research activities are focused on the production and crystallization of neurotrophin receptors in complex with selected compounds. The structural studies will clarify the determinants for ligands binding and hence drive receptor-based drug design.