Seminario del Departamento de Química Biológica

Protein misfolding and aggregation are common events in a wide variety of neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease (PD). Aging is the major known risk factor for the development of neurodegenerative diseases, but mutations in several genes are associated with familial forms. In PD, aggregation of alpha-synuclein (ASYN) in Lewy bodies and the loss of dopaminergic neurons from the substantia nigra, are typical pathological hallmarks. Our limited understanding of the molecular mechanisms underlying protein aggregation and neurodegeneration has complicated both early diagnosis as well as the development of novel therapeutic approaches. Therefore, efforts to integrate different levels of biological information are necessary to improve disease definition. In our studies, we exploit different model organisms and employ diverse molecular approaches to unravel the molecular basis of neurodegenerative disorders. We are using novel cellular models where central aspects associated with ASYN dysfunction are recapitulated and we are now using powerful imaging approaches to investigate how different types of protein-protein interactions influence conformational changes in ASYN and how those relate to the initial oligomerization events associated with its toxicity. Altogether, our approaches will contribute for the development of novel strategies for therapeutic intervention in protein misfolding disorders.