Scientists from the Gladstone Institutes in San Francisco, California, together with collaborators from Stanford, UCSF, Buck Institute for Research on Aging, and UCSD, have discovered that salsalate, a drug used to treat rheumatoid arthritis and a chemical relative of aspirin, effectively reversed tau-related dysfunction in an animal model of frontotemporal dementia (FTD). Salsalate prevented the accumulation of tau in the brain and protected against cognitive impairments resembling impairments seen in Alzheimer's disease and FTD. Salsalate inhibits tau acetylation, a chemical process that can change the function and properties of a protein. In results published online on September 21, 2015 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 toxic 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. The Nature Medicine article is titled “Critical Role of Acetylation in Tau-Mediated Neurodegeneration and Cognitive Deficits.” "We identified, for the first time, a pharmacological approach that reverses all aspects of tau toxicity," says co-senior author Li Gan, Ph.D., 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.
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