Arthritis drug may treat Alzheimer’s disease
Salsalate, a drug used to treat rheumatoid arthritis, may reverse the effects of Alzheimer’s disease and frontotemporal dementia (FTD), says scientists from the Gladstone Institute.
Published in Nature Medicine, the researchers revealed that acetylated tau is a particularly toxic form of the protein, driving neurodegeneration and cognitive deficits. Salsalate successfully reversed these effects in a mouse model of FTD, lowering tau levels in the brain, rescuing memory impairments, and protecting against atrophy of the hippocampus–a brain region essential for memory formation that is impacted by dementia.
“We identified for the first time a pharmacological approach that reverses all aspects of tau toxicity,” says co-senior author Li Gan, PhD, an associate investigator at the Gladstone Institutes. “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.”
Although tau has been a target in dementia research for some time, there are no tau-targeted drugs available for patients. Additionally, how the protein builds up in the brain, causing toxicity and contributing to disease, still remains largely a mystery.
The Gladstone scientists discovered that salsalate can inhibit the enzyme p300 in the brain, which is elevated in Alzheimer’s disease and triggers acetylation. Blocking tau acetylation in this way enhanced tau turnover and effectively reduced tau levels in the brain. This reversed the tau-induced memory deficits and prevented loss of brain cells.
“Targeting tau acetylation could be a new therapeutic strategy against human tauopathies, like Alzheimer’s disease and FTD,” says co-senior author Eric Verdin, MD, a senior investigator at the Gladstone Institutes. “Given that salsalate is a prescription drug with a long-history of a reasonable safety profile, we believe it can have immediate clinical implications.”
The scientists say further clinical studies to test salsalate are already initiated.
Category: Features, Pharmaceuticals
