03 Dec Algernon? Scientists Use Drug to Reverse Memory Loss in Mice
MedicalResearch.com Interview with:
Susanna Rosi, Ph.D.
Lewis and Ruth Cozen Chair II
Professor, Brain and Spinal Injury Center
Weill Institute for Neuroscience
Kavli Institute of Fundamental Neuroscience
Departments of Physical Therapy Rehabilitation Science,
University of California San Francisco
MedicalResearch.com: What is the background for this study?
Response: Everybody has experienced a “senior moment” forgetting where the car keys are, or where you put your glasses. These forgetful moments are not always indicative of a disease, but rather can be a consequence of normal aging. Normal aging is associated with decline of cognitive abilities, such as memory, spatial orientation, problem solving and executive functioning. Investigating what changes happen in the brain with age, can help us to understand why these ‘senior moments’ occur. When we understand what causes these moments, we can design therapeutics with the hopes of preventing or reversing them.
With increased life expectancy age-associatedmemory decline becomes a growing concern.
We wanted to investigate
(i) What causes memory decline with age?
(ii) Are there ways to reverse it?
MedicalResearch.com: What are the main findings?
Response: The integrated stress response (ISR) is a conserved mechanism that all cells use to cope with environmental stress. The ISR is activated in the brain during aging. By studying old male and female mice our studies demonstrated that treatment with the drug-like small-molecule ISR inhibitor ISRIB reverses ISR activation in the brain. ISRIB treatment reverses spatial memory deficits and ameliorates working memory in old mice. When we analyzed the brain region responsible for learning and memory and found that ISR inhibition rescues:
- Neuronal function
- Neuronal structures and
- Immune response.
Thus, pharmacological interference with the ISR emerges as a promising intervention strategy for combating age-related cognitive decline in otherwise healthy individuals.
MedicalResearch.com: What should readers take away from your report?
Response: Aging is an inevitable process for all living creatures, improving our understanding of cellular and molecular processes associated with healthy aging can allow for intervention strategies to reverse unwanted side-effects such as cognitive decline. Now that we have identified the therapeutic potential of ISR inhibitors in rodents, the next step will be to uncover if similar restorative properties are found in higher level mammals, such as humans.
Karen Krukowski, Amber Nolan, Elma S Frias, Morgane Boone, Gonzalo Ureta, Katherine Grue, Maria-Serena Paladini, Edward Elizarraras, Luz Delgado, Sebastian Bernales, Peter Walter, Susanna Rosi. Small molecule cognitive enhancer reverses age-related memory decline in mice.eLife, 2020; 9 DOI: 10.7554/eLife.62048
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