生物谷综合报道:人到了老年就会容易健忘,如何能够让大脑细胞一直受到刺激保持记忆能力是科学家们最关注的研究课题之一。最近,美国新泽西州鲁特杰斯大学的几位科学家表示,他们已经发现了一种能够刺激脑细胞增长的蛋白质,模仿这种蛋白质的化学成份制成药物将可以起到增强记忆的效果。
上述科学家表示,这种蛋白质富含的化学成份“cypin”是大脑进行学习和记忆存储时最需要的物质之一,另外其在不同脑细胞之间建立连接方面也扮演着重要的角色。
科学家称,完全可以基于“cypin”研发出类似的增强记忆药物。科学家之一鲍妮-菲雷斯坦教授表示,“cypin”看起来对于脑神经细胞之间的细丝状连接物的增长起着至关重要的作用,而这些细丝状连接物正是记忆形成的原因之一。她说,当神经细胞之间无法连接时,大脑可能就会出现记忆渐渐缺失等症状,最明显的反映就是老年痴呆病人的症状。
菲雷斯坦教授说:“确定‘cypin’的作用以及了解它的工作原理将为治疗严重的脑神经紊乱打开新的途径。‘cypin’可以说是刺激脑神经细胞增长的催化剂,如果说神经细胞是一颗树,‘cypin’就是树干生长的控制器。树干生长越好越枝繁叶茂,神经细胞就能够接收更多的信息从而增强大脑的记忆能力。”
科学家表示,“Cypin”这种化学成份早在1999年已经被发现,但直到最近才被确认是大脑内部一种活跃的生化酶。
这是1999年发表在Neuron上的文章:
Neuron. 1999 Nov; 24(3): 659-72.
Cypin: a cytosolic regulator of PSD-95 postsynaptic targeting.
Firestein BL, Firestein BL, Brenman JE, Aoki C, Sanchez-Perez AM, El-Husseini AE, Bredt DS.
Department of Physiology, University of California, San Francisco 94143, USA.
Postsynaptic density 95 (PSD-95/SAP-90) is a membrane associated guanylate kinase (GK) PDZ protein that scaffolds glutamate receptors and associated signaling networks at excitatory synapses. Affinity chromatography identifies cypin as a major PSD-95-binding protein in brain extracts. Cypin is homologous to a family of hydrolytic bacterial enzymes and shares some similarity with collapsin response mediator protein (CRMP), a cytoplasmic mediator of semaphorin III signalling. Cypin is discretely expressed in neurons and is polarized to basal membranes in intestinal epithelial cells. Overexpression of cypin in hippocampal neurons specifically perturbs postsynaptic trafficking of PSD-95 and SAP-102, an effect not produced by overexpression of other PDZ ligands. In fact, PSD-95 can induce postsynaptic clustering of an otherwise diffusely localized K+ channel, Kv1.4. By regulating postsynaptic protein sorting, cypin may influence synaptic development and plasticity.
这是另一个最新相关报道,最新有关cypin文章发表在Nature neurosciences
Rutgers scientists discover protein in brain affects learning and memory
NEW BRUNSWICK/PISCATAWAY, N.J. – Rutgers researchers have discovered what could be the newest target for drugs in the treatment of memory and learning disabilities as well as diseases such as Alzheimer's and fetal alcohol syndrome: a protein known as cypin.
Cypin is found throughout the body, but in the brain it regulates nerve cell or neuron branching. Branching or dendrite growth is an important process in normal brain function and is thought to increase when a person learns. A reduction in branching is associated with certain neurological diseases.
"The identification of cypin and understanding how it works in the brain is particularly exciting since it opens up new avenues for the treatment of serious neurological disorders," said principal investigator Bonnie Firestein, assistant professor of cell biology and neuroscience at Rutgers, The State University of New Jersey. "This paves the way to designing new drugs that could target this protein molecule."
Proteins or the genes that code for them have become the targets of choice for developing precisely focused, effective new drug therapies – one of the outcomes of the many revelations provided by the Human Genome Project.
Firestein first identified and isolated cypin in 1999 during her postdoctoral research. She is currently focusing on how it works in the hippocampus, a structure in the brain associated with the regulation of emotions and memory.
"We knew that cypin existed elsewhere in the body where it performs other functions, but no one knew why it was present in the brain," Firestein. Her new research determined that cypin in the brain works as an enzyme involved in shaping neurons.
"One end of a neuron looks like a tree and, in the hippocampus, cypin controls the growth of its branches," she explained. "An increase in the number of branches provides additional sites where a neuron can receive information that it can pass along, enhancing communication."
Maxine Chen, a graduate student in Firestein's laboratory, helped substantiate the connection between cypin and dendrite growth. When she looked closely at neurons in the lab, she found cypin only in certain neurons – "neurons that tended to be more fuzzy," as she described those with increased dendrites. Stimulating neurons in a dish also produced an increase in the protein overall. This has been shown to increase dendrite growth.
Fellow graduate student Barbara Akum further verified the connection between the protein and branching. She used a new molecular technique developed by Samuel Gunderson, a Rutgers assistant professor of molecular biology and biochemistry. With this new tool, Akum reduced the expression of cypin and observed a consequent decrease in branching.
"We also found something else that is really exciting," said Firestein, referring to the molecular mechanics by which cypin affects dendrite growth. Cypin appears to act as a glue that cements other molecules together into long chain structures that extend through the branches of a dendrite as a skeleton.
"Cypin works on tubulin, a protein that is a structural building block of the dendrite skeleton," explained Firestein. "If you just take our purified protein and mix it with tubulin in a test tube, the cypin on its own will actually cause these skeletal structures to grow."
A paper presenting this research will appear in Nature Neuroscience online beginning (Sunday) Jan. 19.