eLife: Small molecule ISR inhibitors are expected to return the brain to old age

In a new study, Karen Krukowski et al. expanded the use of ISRIB: using it to rapidly reverse spatial memory defects and improve working memory in preclinical models of aging in mice.
only need to inject ISRIB three times a day, older mice can perform better in radial arm water maze.
older mice treated with ISRIB also showed better cognitive performance in the delayed matching experimental paradigm after 18 days of treatment with ISRIB.
effects were not seen in young mice in the control group, suggesting that the improvement induced by ISRIB was age-dependent.
at the cellular level, ASRIB can save the electrophysiological properties of neurons and restore spinal density measured by confocus imaging, as shown by the whole cell patch clamping.
quantitative PCR analysis of the sea mass obtained from mice treated with ISRIB showed that inflammatory molecules and T-cell markers associated with interferon (IFN) were reduced to similar concentrations in young mice.
these results suggest that the elderly brain may still be able to maintain basic cognitive abilities, but may be caught in a vicious cycle of cellular stress.
ISR-based drug weakening is a promising strategy to break this vicious cycle and restore cognitive impairment over time.
, however, these ISRIB-mediated neural and immune effects were only tested in male mice.
further research is needed to see if these recovery effects can also be observed in female mice.
important is whether ISRIB can produce similar effects in large animals that are more biologically similar to humans.
: 1.Su Xinyi. Brain rejuvenation by inhibiting stress response. Science Translational Medicine, 2020, doi:10.1126/scitranslmed.abf7740. 2.Karen Krukowski et al. Small molecule cognitive enhancer reverses age-related memory decline in mice. eLife, 2020, doi:10.7554/eLife.62048.