α-Synuclein triggers cofilin pathology and dendritic spine impairment via a PrP^C-CCR5 dependent pathway.

ABSTRACT: 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. In vivo, cofilin pathology is present concomitantly with synaptic impairment and cognitive dysfunction. Rods generation prompted by αSyn involves the co-action of the cellular prion protein (PrP^C) and the chemokine receptor

SUBMITTER: Oliveira da Silva MI 

PROVIDER: S-EPMC11016063 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature