Old drugs are new! Antineoplastic drugs or treat autism | Nature Supplement
March 16, 2018 Source: Biological Exploration
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];At present, drug treatment has not been able to change the course of autism, and it lacks specific drugs for treating core symptoms. Existing drugs can only improve some emotional and behavioral symptoms of patients. Recently, an article published in the journal Nature Neuroscience stated that an anti-tumor drug may be used to reverse social defects associated with autism spectrum disorder (ASD).
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One of the strategies for the development of anticancer drugs is to effectively isolate genes so that they can be expressed again, such as romidepsin, which can effectively inhibit histone deacetylases (HDACs), modify histones, and reshape stains. Quality, regulating the transcription of targeted genes.
According to scientists at the University of Buffalo, genes affected by romidepsin act on both cancer and autism. Short-term treatment with a very low dose of romidepsin in a mouse model of autism with a defect in the Shank3 gene can sustainably inhibit their social deficits.
The effects of this drug lasted for three weeks in mice, from the adolescent age of the mouse model to the late teens, which is equivalent to a few years of humans. This period is also a critical stage of social closure, and the results indicate Romydi Xin has a long-lasting therapeutic effect on autism.
1. Romidepsin alleviates social defects
In the autistic mouse model, HDAC2 is abnormally high, making chromatin in the nucleus very tight, preventing the entry of genetic material into the transcriptional machinery that requires expression.
"HDAC inhibitors can relax high-density chromatin, allowing transcriptional machinery to enter the promoter region of the gene; therefore, they can be expressed, and once HDAC2 is upregulated, it reduces genes that should not be inhibited and leads to behavior Changes, such as autism-like social deficiencies, explains Dr. Zhen Yan, professor of physiology and biophysics at the State University of New York at Buffalo.
The transient treatment with romidepsin attenuated the social deficiencies of shank3-deficient mice. "By upregulating HDAC2 transcription in these mice and then knocking out HDAC2 in the prefrontal cortex with romidepsin, they can save their social deficits," the authors of the article noted.
An early study by Dr. Yan and colleagues revealed how blocking neural communication by affecting the function of the NMDA (n-methyl-d-aspartate receptor) receptor leads to a common social defect tendency in ASD. Key factors that regulate cognition and emotions.
The researchers described in detail how increased nuclear localization of β-catenin, a Shank3 binding protein that regulates cell adhesion and transcription, in Shank3-deficient mice induces up-regulation of HDAC2 and leads to social defects. The authors stated, "At the downstream molecular level, romidepsin treatment increased expression of Grin2a and actin regulatory genes and histone acetylation, and restored NMDA receptor function and actin filaments in Shank3-deficient mice. ."
2 , the general effect of romidepsin
"Autism involves the loss of many genes," Dr. Yan said. "To save this social deficiency, there must be a compound that affects all kinds of genes involved in neural communication."
"The fact that genes with autism and cancer risk are widely overlapping, many of which are chromatin remodeling factors, also demonstrates that epigenetic drugs for cancer treatment are targeted therapy for autism. The necessity."
When Dr. Yan and her co-authors conducted a genome-wide screening, they found that romidepsin restored more than 200 genes that they used to suppress animal models of autism.
3. Important research results
"The ability to adjust a set of key genes identified as triggering autism may explain the power of this drug for autism," Dr. Yan said. "The results of this study highlight the society associated with the Shank3 gene defect. The epigenetic mechanism of defects, which may suggest a potential therapeutic strategy for autistic patients with Shank3 mutations."
References: 1) Autism-Like Social Deficits Reversed by Epigenetic Drug
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