IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Neuronal expression of NUsc1, a single-chain variable fragment antibody against Ab oligomers, protects synapses and rescues memory in Alzheimer´s disease models
Autor/es:
MARÍA CLARA SELLÉS; ANDRE BITENCOURT; ADRIANO SEBOLLELA; FERNANADA DE FELICE; JULIANA FORTUNA; AMANDA SOUZA; OTTAVIO ARANCIO; JERUSALINSKY, DIANA ALICIA; CERCATO, MAGALÍ; VANIA PRADO; WILLIAM KLEIN; SERGIO FERREIRA
Reunión:
Congreso; The 10th IBRO World Congress of Neuroscience; 2019
Institución organizadora:
International Brain Research Organization & Federation of Asian-Oceanian Neuroscience Societies
Resumen:
Alzheimer?s disease (AD) is the main cause of dementia in the elderly and is characterized by abnormal accumulation of the amyloid-β peptide (Aβ) in the brain. Considerable evidence implicates soluble Aβ oligomers (AβOs) in synapse dysfunction and memory loss in AD. Here, we have investigated the neuroprotection conferred by neuronal expression of NUsc1, a single-chain variable fragment (scFv) antibody that specifically targets AβOs, with low reactivities against Aβ monomers and fibrils. Purified recombinant NUsc1 prevented AβO-induced inhibition of synaptic plasticity in hippocampal slices and blocked memory impairment in mice that received an intracerebroventricular (i.c.v.) infusion of AβOs. Sustained neuronal expression of NUsc1 was achieved using an adenoassociated virus-derived vector (AAV-NUsc1). AAV-mediated NUsc1 expression significantly reduced Aβ! O binding to hippocampal neurons in culture, and prevented AβO-induced loss of dendritic spines. In vivo, AAV-NUsc1 induced brain expression and secretion of NUsc1, and rescued memory in aged APPswe/PS1dE9 AD model mice and in wild type mice that received an i.c.v. infusion of AβOs. Finally, AAV-NUsc1 induced NUsc1 expression in adult human brain slice cultures. Results suggest that AAV-NUsc1 may represent a potential tool for gene therapy aimed at preventing synapse damage and memory defects in AD.