Molekulare Drehtür: Der Protonentransport in einem künstlichen molekularen Protonenkanal kann in Moleküldynamiksimulationen an‐ und ausgeschaltet werden, und ein Rückfluss lässt sich verhindern. Wie in entsprechenden biologischen Systemen dienen eine rotierbare funktionelle Gruppe an der Innenwand einer Nanopore als Steuerelement und ein externes elektrisches Feld als Energiequelle. Die Aufnahme und Abgabe eines Protons führen zum Öffnen und Schließen des Steuerelements.
Adult neurogenesis declines with age due to the less functional neural stem cells (NSCs) and niches, but the underlying molecular bases for this impaired condition remain unclear. Here we analyzed >55,000 single-cell transcriptomes from two discrete neurogenic niches across the mouse lifespan, and identified new features and populations in NSCs, new markers and neurogenic regional-specific alternations during aging. Intercellular communication analysis revealed defects in brain-derived neurotrophic factor (BDNF)-TrkB signaling cascade in old NSCs. Carboxypeptidase E (CPE) was found to be highly enriched in NSCs, and played a crucial role in mature/pro-BDNF balance and adult neurogenesis. Diminishment of CPE with aging resulted in impaired generation of BDNF, thus limiting the neurogenesis in old neurogenic niches. Restoring CPE expression markedly rescued the adult neurogenesis by increasing the production of mature BDNF, offering an attractive therapeutic strategy for the treatment of certain disorders in regions associated with constitutive neurogenesis.
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