BMI Seminar // Synaptotoxicity in Alzheimer’s disease: a new therapeutic target
Event details
Date | 20.12.2017 |
Hour | 12:15 › 13:15 |
Speaker | Alain Buisson, Neuropathologies and Synaptic Dysfunctions, Neurosciences Institute, Grenoble, France |
Location | |
Category | Conferences - Seminars |
Alzheimer’s disease (AD) is a neurodegenerative disease that affects memory. A large body of evidence has implicated Amyloid β1-42 protein (Aβ) and other cleavage products of the amyloid precursor protein (APP) as central to synaptic plasticity disruption. Similarly fibrillar deposits of phosphorylated tau are a characteristic feature of several neurodegenerative diseases including AD. Tau is a microtubule-associated protein well known for its stabilization of microtubules in axons. Recently, it has emerged that tau participates in synaptic function as part of the molecular pathway leading to Aβ-driven synaptotoxicity in the context of AD. In this presentation, I will describe the implication of tau in the profound functional synaptic modification associated with synaptic plasticity and how AD mimicking conditions induce a mislocalization of tau into the post synaptic sites of excitatory synapses. We focused on 4 isoforms of human neuronal APP: APP695 Wild-type (APPwt) and APP695 Swedish (K670N/M671L) (APPswe) that both increase Aβ production; APP695 Osaka (E693Δ) (APPosa) which induces an intracellular accumulation of Aβ; and APP695 Icelandic (A673T) (APPice) a mutant that decreases Aβ production and allegedly protects against AD. I will further describe the consequence of the expression of different pathologic mutants of APP, which promote contrasting profile of productions of Aβ, in order to define their impact on the morphology and function of excitatory synapses. Together, these results will highlight the central role of excitatory synapses dysfunctions in the physiopathology of AD.
Practical information
- Informed public
- Free
Organizer
- SV BMI Hosts : J. Gräff & H. Lashuel