miRNA-431 Prevents Amyloid-β-Induced Synapse Loss in Neuronal Cell Culture Model of Alzheimer's Disease by Silencing Kremen1.

摘要: Synapse loss is well regarded as the underlying cause for progressive decline of memory function over course Alzheimer's disease (AD) development. Recent observations suggest that accumulation Wnt antagonist Dickkopf-1 (Dkk1) in AD brain plays a critical role triggering synaptic degeneration. Mechanistically, Dkk1 cooperates with Kremen1 (Krm1), its transmembrane receptor, to block Wnt/β-catenin signaling pathway. Here, we show silencing Krm1 miR-431 prevents amyloid-β-mediated synapse cortico-hippocampal cultures isolated from triple transgenic 3xTg-AD mice. Exposure AβDDL (an amyloid-β derived diffusive ligand) or reduced number pre- and post-synaptic puncta primary neuronal cultures, while treatment prevented loss. In addition, also neurite Our findings demonstrate protects synapses neurites Aβ-toxicity an cell culture model may be promising therapeutic target.