Rheumatoid Arthritis Drug Shows Potential For Alzheimer's

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An old drug, salsalate, that is used to treat rheumatoid arthritis has also showed promise as a potential therapy for Alzheimer’s disease as the medication prevented the accumulation of dangerous tau protein in the brain in an animal model.

Li Gan, PhD, of the Gladstone Institutes, San Francisco, and colleagues found that  salsalate blocks tau acetylation, a chemical process that can change the function of a protein. Acetylated tau promotes neurodegeneration and cognitive deficits.

In a mouse model, salsalate reversed the effects of acetylated tau in a mouse model of frontotemporal dementia by lowering levels of tau in the brain, improving memory impairment and protecting against deterioration of the hippocampus, a part of the brain critical for memory formation, the researchers wrote in Nature Medicine.

“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,” Gan said in a statement.

After looking at post-mortem brains with Alzheimer’s disease, researchers found that tau acetylation is one of the first signs of pathology, even before tangles are deformed. The acetylated tau was a driver for tau accumulation and toxicity.

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In a mouse model, salsalate reversed the effects of acetylated tau by lowering levels of tau in the brain.

Scientists from the Gladstone Institutes have discovered that salsalate, a drug used to treat rheumatoid arthritis, 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. 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.

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