The usual approach for developing treatments for brain disorders is to make a drug that acts on a specific molecular target. But this approach has largely failed. In this episode I talk with Professor Raj Ratan at Weill Cornell Medicine about ways to tap the intrinsic ability of brain cells to respond adaptively to challenges – metabolic, oxidative, and biosynthetic – in ways that protect them against pathological processes such as those occurring in stroke, traumatic brain injury, Alzheimer’s and Parkinson’s diseases. Raj and his colleagues have developed several different interventions that are highly effective in animal models of stroke and Alzheimer’s disease. Intermittent dosing with such treatments can activate evolutionarily conserved complex and integrated gene expression responses in brain cells that bolster stress resistance and enable recovery and repair.

LINKS

Dr. Ratan’s laboratory webpage: https://burke.weill.cornell.edu/ratan-lab/people/rajiv-r-ratan-md-phd

Selenium protects against ferroptosis and stroke:

https://www.cell.com/action/showPdf?pii=S0092-8674%2819%2930327-7

HIF prolyl hydroxylase inhibition for stroke ?:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390817/pdf/jcbfm201228a.pdf

2-deoxyglucose for experimental stroke and Alzheimer’s disease:

https://pdf.sciencedirectassets.com/272195/1-s2.0-S0896627322X00196/1-s2.0-S0896627323004725/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEDMaCXVzLWVhc3QtMSJHMEUCIC02vyvj45WOEJ6cJ%2BO3zLTkbyrmywu3UV2k0tE99ISSAiEAm%2B2Ga7NWSJSMResvqmDJZn87epQuNnoQNFUS%2FM1xh1QquwUIvP%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FARAFGgwwNTkwMDM1NDY4NjUiDKWhJaRjapFKYPcUuSqPBXZt7z6Y%2F%2FFQDTJZNd63uYfGqFnqQ5FraRDyTiOoShRDuHZ%2FFurOQBeXcKh34xKHbYXG3aw4aZ1qknn5rmr5oZKXJEnQKSDQbTIMaZfam7JN223W98JHQjFExQSg1IpIXsJIOpPDRC6SnxewO9HWfK5VsT22Yd1%2FvfyJ6TNHysLd5avZUcCzNwd1Tzg%2F7n5boUZ3bv8ksKJTbXKIa6URMIpJ1Elry%2Bx2cOHHsudyKQHl38MnqJfyBDlsvlSdlvPvqZyiDl41UPQ4wQXG8zxZKtwc4W9Nz3bBDtosARXGGykFw5PGjP8vljwzBmpAIPA2vntVuzKB1GVCjSOPeZIfB%2FT7gbpjO6XFPulqMJfoZSHMIP6U5%2Baluyz25U7gQI0DlHQuqHHQlPp16W1%2FZUDpV6qfCWLDFa86hE3Mk2bUdhVxC7%2F1avNNvRjCVubyOhIY9MrjdQSpJx5FCd9yj2KkOAQSxn0T8ZQ2HZl10eOzNJBv0flA%2BQXys58UySTYb0QHKIOrD1YbjW0M%2B1qrdzwunAYlpugxnqm64BMuZL1aUWPQUzD6Xu59k23wj9IKZ7ysz8OJgHiaxCL%2BmrhMtF1wBO5rkKomJdordmx%2B46wjknrwW9sUy4NFS74JkUYhIGjiZ1lQ6E%2BFcjJe1R%2FeLOfxx2VfcbXyzyjaVgNaS16fRYydqoT0r1xth2rMdDADuFYvT1Mxw909AAZ6ja4ur%2Bcb56eAT7kbwtKDDsTq3l%2FlTVEwX8zAkagg%2Ba2yg2RUF26zTiA9ur%2FR1keAROBxVFyOyhBFg0tX2aHFaPkRmbTLOOeslpmFdWYlYhhLn%2FDgHzXafbqJ6MS29hnDJVpSZNwtkILsv6Fvf7MlT%2FU%2Fdet6sI4w6oKBswY6sQGQdr%2Fyh54qyfoNjp7vTeWRp56lw26rZzdq5JzhPL7AooWioriINJoD5PBTfQ6P9kkjgrbt3KgE0gLwdquV5t8cPemG6Ud6J7FFfiCqdduYGnkdgvqay00lKumUQWivFmbLK1KwV3ZTiHqK6k%2BnwmjmJx6TC2wOb0ri18vlPuaf9tL3twxztVgBXpqCEHtrk2xoln3A%2FxRta1ENiKDj3i%2BeEJsq8LA5%2Ft1DnHnQTTngNeI%3D&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20240605T120054Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTYTBFTALVN%2F20240605%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=a28ce7980230f4e238a2b9b01639b4a3771986228a5b71afee77812caae7ec5a&hash=2c8062367af976e82b072e2c70fee70c72e3b4c101e00ffb8e600353969e084d&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&pii=S0896627323004725&tid=spdf-39789cb0-1edf-4028-964c-0b8b685189bb&sid=957e62f0674d764d5259d1032c07123fda92gxrqa&type=client&tsoh=d3d3LXNjaWVuY2VkaXJlY3QtY29tLnByb3h5MS5saWJyYXJ5LmpodS5lZHU%3D&ua=0f105b59005f5e555053&rr=88f00141e8697283&cc=us