Marina I Oliveira da Silva, Miguel Santejo, Isaac W Babcock, Ana Magalhães, Laurie S Minamide, Seok-Joon Won, Erika Castillo, Ellen Gerhardt, Christiane Fahlbusch, Raymond A Swanson, Tiago F Outeiro, Ricardo Taipa, Michael Ruff, James R Bamburg, Márcia A Liz
Cognitive dysfunction and dementia are critical symptoms of Lewy Body dementias (LBD). Specifically, alpha-synuclein (αSyn) accumulation in the hippocampus leading to synaptic dysfunction is linked to cognitive deficits in LBD. Here, we investigated the pathological impact of αSyn on hippocampal neurons. We report that either αSyn overexpression or αSyn pre-formed fibrils (PFFs) treatment triggers the formation of cofilin-actin rods, synapse disruptors, in cultured hippocampal neurons and in the hippocampus of synucleinopathy mouse models and of LBD patients...
April 13, 2024: Cell Death & Disease