Engineering a neuronal cell lineage to produce a single chain antibody against toxic oligomers of beta-amyloid peptide

Abstract

Toxic soluble beta-amyloid oligomers (AbetaOs) are pivotal toxins responsible for the synaptic loss and cognitive impairment in brain diseases such as Alzheimer's disease. As a result, the interaction between these oligomers and neurons became a strategic target for the development of new therapeutic interventions. However, the structure of these toxic species is yet not known, as well as the molecular mechanisms by which oligomers cause neuronal damage. The main goal of our laboratory is to understand the molecular basis of protein oligomers toxicity associated with Alzheimer's Disease, using as main tool artificial humanized scFv type antibodies, capable of distinguishing between non-toxic and toxic oligomers. In this project, we will seek to create a human neuroblastoma cell line that secretes an anti-Abeta oligomer scFv, named NUsc1, previously characterized by our group. We will test the efficiency and selectivity of this antibody produced endogenously in protecting against the neurotoxicity elicited by AbetaOs. We hope that a new strategy with high therapeutic potential against Alzheimer's disease, still a cureless pathology, derive from our study. (AU)