Molecular basis of the toxicity of protein oligomers associated to brain amyloidosis

Abstract

Toxic protein oligomers are believed to be the main culprit for the synaptic loss and cognitive decline in proteinopathies afflicting the central nervous system (CNS), as Alzheimer's, Parkinson, and prionoses. As a result, the interaction between oligomers and neurons is now seen as a preferential target for the development of novel therapeutic strategies against these neuropathologies. On the other hand, detailed structure of these toxic species is still unknown, as the molecular events underlying oligomer-elicited neurotoxicity. Here our main goal is to understand the molecular and cellular mechanism linked to the neurotoxicity of protein oligomers associated to diseases. The experimental approach is centered on the use of novel human single chain antibodies able to distinguish toxic oligomers from their non-toxic assemblies’ counterparts. The work will focus on determining the neuroprotection of anti-oligomer scFv's exhibiting distinct specificities for each oligomeric assembly on both in vitro and in vivo models of CNS. Through this approach we hope to significantly contribute to the development of reagents with therapeutic and diagnostic potential against these devastating and still cureless diseases. (AU)