Scientists have discovered the rheumatoid arthritis drug salsalate reverses tau-related dysfunction in an animal model of frontotemporal dementia (FTD), potentially offering new hope for Alzheimer's patients.
Salsalate inhibits tau acetylation, which is a chemical process that can change the properties of certain proteins, and may play a role in Alzheimer's disease, the Gladstone Institutes reported. Acetylated tau was shown to cause neurodegeneration and cognitive deficits, but salsalate proved to effectively reverse these harmful effects in a mouse model of FTD.
"We identified for the first time a pharmacological approach that reverses all aspects of tau toxicity," said co-senior author Li Gan, 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."
Scientists have been looking at tau as the driver of dementia for some time now, but there are currently no drugs available that effectively target the protein. This new therapy was shown to reduce tau levels in the brain, restore memory, and protect against hippocampus atrophy in the mouse models. Salsalate can inhibit the enzyme p300 in the brain, which is elevated in cases of Alzheimer's disease and can lead to acetylation. Blocking tau acetylation using the arthritis drug proved to enhanced tau turnover and reduce tau brain levels, in turn reducing tau-induced memory deficits and 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,, 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 findings were published in a recent edition of the journal Nature Medicine.