"Amyoid and Tau: the Trigger and Bullet in Alzheimer’s Disease Pathogenesis"
George S. Bloom - University of Virginia, USA (USA )
Gonzalo Ferreira - Universidad de la República. Medicina, Biofísica. Laboratorio Canales Iónicos (Uruguay)
| Conferencista invitado
Amyoid and Tau: the Trigger and Bullet in Alzheimer’s Disease Pathogenesis (#0080)
George Bloom 1
1 - University of Virginia. Depts of Biology, Cell Biology and Neuroscience.
A major obstacle to pre-symptomatic diagnosis and disease-modifying therapy for Alzheimer’s disease (AD) is an inadequate understanding of the molecular mechanisms of AD pathogenesis. For example, impaired brain insulin signaling is an AD hallmark, but whether and how it might contribute to the synaptic dysfunction and neuron death that underlie memory and cognitive impairment has been mysterious. Neuron death in AD is often caused by cell cycle re-entry (CCR) mediated by amyloid-β oligomers (AβOs) and tau, the precursors of plaques and tangles. We have found that CCR results from AβO-induced activation of the protein kinase complex, mTORC1, at the plasma membrane and mTORC1-dependent tau phosphorylation, and that CCR can be prevented by insulin-stimulated activation of lysosomal mTORC1. AβOs were also shown previously to reduce neuronal insulin signaling. Our data therefore indicate that the decreased insulin signaling provoked by AβOs unleashes their toxic potential to cause neuronal CCR, and by extension, neuron death 

Contacto: gsb4g@virginia.edu