在调控神经细胞和协调整体大脑功能的蛋白质中，有一半在预防由中风导致的长期损伤中起着决定性的作用。在美国，中风已成为引起残疾的罪魁祸首，同时也是引起死亡的第三大病因。
据最近发表在《Journal of Neuroscience》上的一项研究，细胞生物学和神经学家Bonnie Firestein说，我们进行了一项新研究，主要致力于研究cypin 和PSD-95两种蛋白质的合成，已取得了相当不错的成果。
cypin – a主要是通过调控神经细胞和神经元分支来维持正常的大脑功能，这样就可以防止神经细胞在中风初期受损、失去和其他细胞之间的联系，也可以阻止任何继发性的大脑和神经损伤。而PSD-95则可以加速细胞损伤和阻止细胞损伤修复。中风继发性损伤通常出现在中风后的几天甚至是几周，常见的有血液流动减慢、供氧不足、头昏脑涨等。
Firestein说：“虽然我们并不清楚cypin是怎么样或者为什么能在这个过程中起作用，但是我们知道cypin可以帮助神经细胞存活下来。”早在十多年前，Firestein就第一次分离鉴定出了cypin。从那以后，她就一直致力于研究cypin在大脑中的作用机制以及如何才能将它应用于治疗神经性脑损和其他严重的神经失调。
Firestein和他的校友Chia-Yi Tseng在实验室做了一个这样的实验：将神经细胞放在一个盘子中，然后制造了一种“实验性中风”——模仿大量谷氨酸盐释放，结果导致神经细胞受损。
他们的研究目的是如何去阻止中风后的继发性损伤。他们发现，随着cypin量的增加，很多中风后存活下来的神经细胞不会发生继发性损伤，而过多的PSD-95则会杀死它们。
“我们希望这项研究能够帮助人们研发出具有很好疗效的药物来治疗神经细胞损伤、减少由中风引起的长期继发损伤以及其他一些神经性脑损。”（生物探索译）
相关英文论文摘要：
The Role of PSD-95 and Cypin in Morphological Changes in Dendrites Following Sublethal NMDA Exposure
Focal swelling or varicosity formation in dendrites and loss of dendritic spines are the earliest indications of glutamate-induced excitotoxicity. Although it is known that microtubule dynamics play a role in varicosity formation, very little is known about the proteins that directly impact microtubules during focal swelling and dendritic spine loss. Our laboratory has recently reported that the postsynaptic protein PSD-95 and its cytosolic interactor (cypin) regulate the patterning of dendrites in hippocampal neurons. Cypin promotes microtubule assembly, and PSD-95 disrupts microtubule organization. Thus, we hypothesized that cypin and PSD-95 may play a role in altering dendrite morphology and spine number in response to sublethal NMDA-induced excitotoxicity. Using an in vitro model of glutamate-induced toxicity in rat hippocampal cultures, we found that cypin overexpression or PSD-95 knockdown increases the percentage of neurons with varicosities and the number of varicosities along dendrites, decreases the size of varicosities after sublethal NMDA exposure, and protects neurons from NMDA-induced death. In contrast, cypin knockdown or PSD-95 overexpression results in opposite effects. We further show that cypin regulates the density of spines/filopodia: cypin overexpression decreases the number of protrusions per micrometer of dendrite while cypin knockdown results in an opposite effect. Cypin overexpression and PSD-95 knockdown attenuate NMDA-promoted decreases in protrusion density. Thus, we have identified a novel pathway by which the microtubule cytoskeleton is regulated during sublethal changes to dendrites.
英文论文链接:https://www.jneurosci.org/content/31/43/15468.abstract?sid=b987b4a3-5cca-4b30-9e19-5cc82b6e0537
