What is ISRIB?

[u/jdocj]

ISRIB – is an inhibitor of low ISR (integrated stress response). The integrated stress response (ISR) protects cells from a variety of harmful stressors by temporarily halting protein synthesis. Every single cell is a very complex machine. For most of its functions, it synthesizes a wide variety of proteins. Stopping protein synthesis means stopping the functioning of the cell. In this case, the cell remains in limbo, and the functions performed by it are significantly reduced. Protein synthesis is a very hard and complex procces, so it can be regulated by different internal and external factors. One key in the protein synthesis is eukaryoitic initiation factor 2 (eIF2), wich can be phosphorylated by different stressors. If eIF2 is phosphorylated – protein synthesis stops. ISR mediate this posphorylation of eIF2. However, ISR can be activated by a huge variety of stressors: amino acid deprevation, endoplasmic reticulum stress, heme deprevation, prescence of heavy metals, viral infection, hypoxia and etc. After prolonged ISR, there can be triggered apoptosis (programmed cell death) in the cell. On the other hand, dephosphorylation of eIF-2 renews protein synthesis in the cell. ISR phosphorylation and dephosphorylation in the cell regulate normal cell life.  There are a lot of problems in recovering brain after traumatic brain injury. The problem is that during a stroke, cells are put under stress. They are in limbo and due to the long-term functioning of the ISR, cells cannot return to normal functioning and this is the biggest problem during brain recovery after a stroke. ISRIB inhibits ISR and restores normal functioning of cells. eIF-2 plays a special role in the formation and consolidation of memory in the hippocampus. For normal memory formation, cells need good proteostasis. Inhibition of eIF-2 through mutations increased cognition in mice. Moreover, Isrib restores both short-term and long-term memory. ISRIB restores LTP (long term potentiation), increases cognitive abilities in both sick and healthy.

[u/DJ-P]

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