Researchers from the Gladstone Institute have found that Salsalate – a medication that belongs to the salicylate and Non-Steroidal Anti-Inflammatory Drug (NSAID) classes – helps prevent the accumulation of tau in the brain and even cognitive impairment comparable to impairments of Alzheimer’s disease (AD) and Frontotemporal Dementia. (FTD)
“We identified for the first time a pharmacological approach that reverses all aspects of tau toxicity. Remarkably, the profound protective effects of salsalate were achieved even though it was administered after disease onset, indicating that it may be an effective treatment option.” said Co-senior author Li Gan, an associate investigator at the Gladstone Institutes and PhD.
The study was published in the Journal Nature Medicine and was named “Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficit”. Salsalate was first used to treat rheumatoid arthritis, but surprisingly it reversed tau-impairments in an animal model of FTD.
The researchers team stated that salsalate can reduce acetylated tau levels, and rescued memory impairments. Acetylated tau is an unusual form of the point that leads to brain damage. The drug also protected the brain against atrophy of the hippocampus – which is a brain part essential for memory generation and is usually impacted by dementia.
However, the scientist clarified that the capabilities of decomposition that tau accumulates and the resulting causes of neurodegeneration still remain unclear. There are no current tau-targeted drugs available for patients in need.
The Gladstone team investigated post-mortem brains with AD and discovered that tau acetylation is one of the main reasons for the disease. The acetylated tau accelerated the Alzheimer’s disease progression and it also supplied more tau agglomeration and toxicity.
Moreover, Dr.Gan and his team worked in an animal model of FTD and determined that when the tau was acetylated, the neurons tended to reduce the ability to degenerate the protein, causing the accumulation in the brain. As a result, the mice suffered from a cognitive impairment on several separate memory tests.
“Targeting tau acetylation could be a new therapeutic strategy against human tauopathies, like Alzheimer’s disease and FTD. Given that salsalate is a prescription drug with a long-history of a reasonable safety profile, we believe it can have immediate clinical implications.” stated Eric Verdin, co-senior author and senior investigator at the Gladstone Institutes.
To go further with the the investigation, and to also gain a broader understanding, researchers have already started a clinical trial using salsalate to reduce tau levels in progressive supranuclear palsy, which is another tau-mediated neurological condition.
Source: Nature Medicine