分类: 生物学 >> 生物物理学 >> 神经科学 提交时间: 2016-06-06
摘要: Previous studies have shown that the Hippo pathway effector yes-associated protein (YAP) plays an important role in maintaining stem cell proliferation. However, the precise molecular mechanism of YAP in regulating murine embryonic neural stem cells (NSCs) remains largely unknown. Here, we show that bone morphogenetic protein-2 (BMP2) treatment inhibited the proliferation of mouse embryonic NSCs, that YAP was critical for mouse NSC proliferation, and that BMP2 treatment-induced inhibition of mouse NSC proliferation was abrogated by YAP knockdown, indicating that the YAP protein mediates the inhibitory effect of BMP2 signaling. Additionally, we found that BMP2 treatment reduced YAP nuclear translocation, YAP-TEAD interaction, and YAP-mediated transactivation. BMP2 treatment inhibited YAP/TEAD-mediated Cyclin D1 (ccnd1) expression, and knockdown of ccnd1 abrogated the BMP2-mediated inhibition of mouse NSC proliferation. Mechanistically, we found that Smad1/4, effectors of BMP2 signaling, competed with YAP for the interaction with TAED1 and inhibited YAP's cotranscriptional activity. Our data reveal mechanistic cross talk between BMP2 signaling and the Hippo-YAP pathway in murine NSC proliferation, which may be exploited as a therapeutic target in neurodegenerative diseases and aging.
分类: 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间: 2016-05-11
摘要: Microcirculation dysfunction is regarded as one of important pathologies of senility, degeneration, immune disorder and many other diseases. Cerebral circulation insufficiency, energetic dysmetabolism, hypoxia-ischemia and metabolites accumulation in Alzheimer's disease (AD) have a close relation with microcirculation dysfunction. Here, we review microcirculation dysfunction playing an important role in hyperphosphorylation of Tau, A beta aggregation and cognitive impairment induced by accumulation of formaldehyde and D-ribose.
分类: 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间: 2016-05-05
摘要: Mapping the pattern of connectivity between neurons is widely regarded to be critical for understanding the nervous system. GRASP (GFP reconstitution across synaptic partners) has been used as a promising method for mapping neuronal connectivity, but is currently available in the green color only, limiting its potential applications. Here we demonstrate CRASP (CFP reconstitution across synaptic partners), a cyan colored version of GRASP. We validated the system in HEK 293T cells, and generated transgenic Drosophila lines to show that the system could reliably detect neuronal contacts in the brain. Furthermore, we showed that the CRASP signal could be selectively amplified using standard immunohistochemistry methods. The CRASP system adds to the toolkit available to researchers for mapping neuronal connectivity, and substantially expands the potential application of GRASP-like strategies. (C) 2015 Elsevier Inc. All rights reserved.