Commonly used antidepressants known as selective serotonin reuptake inhibitors, or SSRIs, can prevent beta-amyloid aggregation, representing a potential new therapeutic strategy for Alzheimer’s disease, a study suggests.
The study, “Interactions of Selective Serotonin Reuptake Inhibitors with β-Amyloid,” was published in ACS Chemical Neuroscience.
The process of developing and approving new therapies is very expensive, but more importantly, it can take between 10 and 15 years to complete, if it’s successful at all. This is a major disadvantage for those living with progressive diseases that lack effective treatments, such as Alzheimer’s disease.
To more quickly and easily find suitable therapies for these diseases, a more attractive strategy involves testing already approved therapies for new applications, also known as drug repurposing.
To this end, recent studies have suggested that antidepressant medications belonging to the class of SSRIs might improve thinking ability by preventing the aggregation of beta-amyloid molecules.
Based on this evidence, researchers at the University of Waterloo in Canada tested several commonly used antidepressants as potential therapies for Alzheimer’s.
In particular, they evaluated the effects of fluvoxamine (brand name Luvox, among others), fluoxetine (brand name Prozac, among others), paroxetine (brand name Paxil, among others), sertraline (brand name Zoloft), and escitalopram (brand name Lexapro) on beta-amyloid aggregates.
Fluvoxamine and paroxetine were found to be the more potent inhibitors, while escitalopram was the only agent that showed reduced potential to prevent beta-amyloid plaque formation, leading to a 21% inhibition. All other tested SSRIs had the ability to inhibit from 54% to 76% of beta-amyloid aggregation when used at the highest doses.
“These are promising findings for people with Alzheimer’s who are on SSRIs,” Praveen Nekkar, PhD, a professor at the School of Pharmacy at Waterloo and senior author of the study, said in a university press release.
Additional experiments further confirmed that the antidepressants directly bind to beta-amyloid molecules, preventing them from forming toxic aggregates.
These results suggest that these SSRIs may hold therapeutic activity for patients with Alzheimer’s disease.
“These finding may not only highlight benefits for people with depression and Alzheimer’s but can also provide insights to serve as a guide to future drug development to treat the disease,” Nekkar said.
With this information, healthcare providers may rethink treatment approaches for patients who have both depression and Alzheimer’s. In addition, these findings could support the use of SSRIs as an early intervention for people who have a family history of dementia.
“Our results can also inform future drug development,” Nekkar said. “The chemical structure of SSRIs presents a type of blueprint for how to develop a medication that will prevent amyloid beta aggregation.
“We can explore developing new drugs based on that model to treat Alzheimer’s.”
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