EL2-1
Self-organized formation of neural organoids from stem cells
多細胞の自己組織化を利用した神経オルガノイド形成
Eiraku Mototsugu（永樂 元次）
Institute for Frontier Life and Medical Sciences
In vitro generation of functional organ with complex structure is a major challenge of cell biology and developmental biology. Toward this goal, it is a reasonable strategy to recapitulate the ontogeny that is the most efficient and robust process for organogenesis acquired through evolution. In the last few decades, molecular aspects concerning the vertebrate body plan and organogenesis have been actively studied. These efforts have unveiled the key molecules and the molecular cascades involving in the vertebrate organogenesis. We have aimed to clarify molecular and cellular mechanisms underlying organogenesis, and to develop new technologies for in vitro recapitulation, that is, formation of functional organ-like tissue (organoids) from stem cells. We have previously established efficient three-dimensional cultures for generation of mouse and human ES/iPS cell-derived brain and retinal tissue as well as other ectoderm-derived tissues. Based on our past achievements in 3D tissue formations from pluripotent stem cells, we have been attempting to extend our limit of understanding for self-organization phenomena in neural development and advance the culture technology for generation of more complex tissues from ES/iPS cells in a more robust manner. I will talk about recent advances in self-organized formation of neural and non-neural tissues in a dish, and discuss its applications for a future regenerative medicine and drug screening for treatment of neural pathology. | | EL2-2
Treatment of Alzheimer's disease: Current situation and prospect
アルツハイマー病の治療：現状と展望
Ono Kenjiro（小野 賢二郎）
Dept. of Neurol., Showa Univ. Sch. of Med.
Alzheimer disease (AD) is the most common type of dementia, and is currently incurable. The efficacy of existing treatments for AD such as acetylcholinesterase inhibitors is limited to symptom improvement. Research on disease-modifying therapies (DMTs) has conventionally focused on amelioration of CNS pathogenesis. AD is characterized by the accumulation of amyloid plaques formed by the amyloid β-protein (Aβ), a 40-42 amino acid peptide and neurofibrillary tangles, composed of paired helical filaments, the principal component of which is tau. Aβ is the primary component of amyloid plaques, and has been suggested to be responsible for the pathogenesis of AD (amyloid hypothesis). Aβ molecules tend to aggregates to form oligomers, protofibrils (PF), and Aβ fibrils. Although these Aβ aggregates may cause neuronal injury, recent evidence supports the hypothesis that intermediate aggregates of Aβ, such as PF and oligomers play a seminal role in AD (oligomer hypothesis). Thus, the inhibition of the oligomerization of Aβ has been suggested as a possible therapeutic target for the fundamental treatment of AD. Recently, we found that various compounds such as wine-related polyphenols and rifampicin inhibited the Aβ oligomerizaition and reduced neuronal and synaptic toxicities in vitro and in vivo. We summarize here recent efforts to produce DMTs targeting Aβ. |
