第107回 アイセムスセミナー: Dr. Michael Silverman

The architecture of the neuron is such that the tip of the axon can be quite distant from the cell body where many of the cell's components are made. Thus, neurons rely on an elaborate microtubule-based transport system to allow for the shipping of cellular components, such as membrane and secreted proteins, to distal sites within the cell. Emerging evidence suggests that fast axonal transport (FAT) defects are early pathological manifestations of several neurodegenerative diseases including Alzheimer's disease (AD). We have previously shown that soluble amyloid beta oligomers (AβOs), a causative agent of AD, impede FAT of dense core vesicles (DCVs) and mitochondria in cultured hippocampal neurons through a NMDA-glutamate receptor mechanism that is mediated by a tau kinase, glycogen synthase kinase 3β (Decker et al., 2010). AβOs induce hyperphosphorylation of the axonal microtubule- associated protein, tau; however, it remains unclear how this modification disrupts transport. Notably, in our studies, transport defects occurred without concomitant microtubule destabilization, which is usually associated with hyperphosphorylated tau. To determine if tau is required for AβO-induced transport defects, we treated hippocampal neurons from wild type and tau knockout mice with nanomolar concentrations of AβOs and determined that transport defects of DCVs containing brain-derived neurotrophic factor (BDNF) indeed persist in the absence of tau. Thus, transport deficits may result from dysregulation of intracellular signaling cascades that are implicated in AD pathogenesis. Current work in our laboratory is geared towards identifying the signaling mechanisms that negatively affect axonal transport in AβO-treated neurons.

講演者 演題	Dr. Michael Silverman Department of Biological Sciences カナダ サイモンフレーザー大学 外国人特別研究員（JSPSフェロー） 演題：Mechanisms of Axonal Transport Defects in a Cellular Model of Alzheimer's Disease
日時	2012年4月12日（木）10:30-11:30
場所	京都大学 iCeMSコンプレックス1 本館 2階 セミナールーム (A207) アクセスマップ
フライヤー	PDF (110KB)
主催	京都大学 物質－細胞統合システム拠点（iCeMS＝アイセムス）
共催	京都大学医学研究科グローバルCOEプログラム「生命原理の解明を基とする医学研究教育拠点」
連絡先	iCeMS 見学グループ kengaku-g@icems.kyoto-u.ac.jp