Structural dynamics and molecular mechanisms involved in the alpha-synuclein aggregation

Abstract

In spite of the large amount of research conducted regarding neurodegenerative pathologies, there is still no consensus as to the cause of these pathologies from a cellular/molecular point of view. A better comprehension of the molecular mechanisms that take part in several neurodegenerative illnesses (such as Alzheimer's and Parkinson's disease, lateral amyotrophic sclerosis, and so on) can aid in the development of new drugs and treatments. One of the main pathologic characteristics present in all of the previously cited disorders is the present of insoluble protein aggregates. One of these aggregates, known as Lewy bodies, is associated with Parkinson's, Parkinson's dementia, and Lewy bodies dementia. Lewy bodies are made up mainly by the ±-synuclein protein - which presents a variety of conformations: monomeric and unstructured in physiological solution, multimeric (usually helical tetrameric), and cross-² -sheet-rich architecture of aggregates. This research project aims to comprehend the ±-synuclein (native and mutant proteins) structure dynamics, aggregation mechanisms and membrane interaction through computational simulations. For the last two years, Luis Paulo Scott has been financed by Fapesp in his research regarding the understanding of molecules related to neurodegenerative pathologies and aggregate formation through the combination of two different computational methodologies: normal modes analysis and molecular dynamics. Ivet Bahar is a renowned specialist in the study of structural dynamics (functional movements and conformational changes) - at the moment she's the coordinator of a research network: The National Center for Multiscale Modeling of Biological Systems (MMBioS), whose goal is to comprehend the dynamics of biomolecules and macromolecules/systems involved in neuronal communication. This senior sabbatical internship would be a continuation of the 2013 sabbatical internship conducted in France, and it would allow the professional development of Dr. Luis Paulo Barbour Scot in the study of the dynamics of biomolecules regarding neurodegenerative pathologies, hence improving his own research group. (AU)