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開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Analysis of beta-secretase activity using hippocampal slice cultures

  • P2-033
  • 上窪 裕二 / Yuji Kamikubo:1 櫻井 隆 / Takashi Sakurai:1 
  • 1:順天堂大学 / Juntendo University 

β-secretase 1(BACE1) is a transmembrane aspartic acid proteinase that cleaves various substrates such as neuregulins, β-subunits of voltage-gated sodium channel, and amyloid precursor proteins (APPs). BACE1 has multiple functions in various neural physiological process, myelination, synapse formation, and neurite growth. Recent studies showed that BACE1 knockout mice display reduced axonal myelination, subtle behavioural changes with mild impairments in spatial learning and memory, and schizophrenia like behavioral symptoms. Increasing evidence indicates that BACE1 activity is involved in Alzheimer's disease (AD), a progressive neurodegenerative disorder and the most common form of age-dependent dementia. Aβ is the main component of deposits found in the brains of patients with AD. BACE1 activity and generation of Aβ is coupled to neuronal activity, but the molecular basis is unknown. Thus to reveal the basic biochemical, molecular biological, and pharmacological properties of BACE1 and Aβ is necessary not only for elucidation of physiologic role of these but also for drug development. Here, we show the persistent analysis of BACE1 and formation and secretion of endogenous Aβ and sAPPβ in organotypic hippocampal slice cultures. Hippocampal slices prepared from peritnatal rodent and cultured for 1-2 weeks may serve as the long-wanted system, since they are stable for following weeks maintaining their original neural circuits. This study is the first step investigated that secretase activity and Aβ secretion using hippocampal slice culture.

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