ISRIB: The ISR InhiBitor

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In December 2020, a research paper was published that drew a lot of attention.

It involved a molecule that reversed memory deficits in aged mice – even weeks after treatment has stopped.

The treatment involved inhibition of the integrated stress response.

In today’s post, we will explore what the integrated stress response is, review the data presented in new report, and consider what might happen next with this line of research (and be warned, there is quite a bit of biology to kick things off).

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Title: Small molecule cognitive enhancer reverses age-related memory decline in mice.
Authors: Krukowski K, Nolan A, Frias ES, Boone M, Ureta G, Grue K, Paladini MS, Elizarraras E, Delgado L, Bernales S, Walter P, Rosi S.
Journal: Elife. 2020 Dec 1;9:e62048.
PMID: 33258451                  (This report is OPEN ACCESS if you would like to read it)

This report was published in December 2020.

It starts with a quote:

Of the capacities that people hope will remain intact as they get older, perhaps the most treasured is to stay mentally sharp” (Source)

The report then proceeds to describe an experiment in which a small drug-like molecule reverses memory deficits in aged mice, even weeks after treatment has stopped.

Wow! What was the treatment?

The molecule is an ‘integrated stress response‘ (or ISR) inhibitor that has conveniently been called ISRIB (or ISR InhiBitor).

What is ISR and why would the researchers be inhibiting it?

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