Resveratrol Administration Increases Transthyretin Protein Levels, Ameliorating AD Features: The Importance of Transthyretin Tetrameric Stability

Undiscovered Roles for Transthyretin: From a Transporter Protein to a New Therapeutic Target for Alzheimer’s Disease

“…Importantly, recent data showed that the TTR/IDIF complex exhibits improved BBB permeability, as compared to TTR and IDIF alone [103], providing higher Aβ sequestering capacity, and adding to the therapeutic potential of TTR in AD. In a different work, administration of resveratrol, to the AD/TTR+/-mouse model, also produced decreased brain Aβ burden and raised plasma TTR concentrations [104], confirming the stabilization hypothesis, whereas administration of resveratrol to a different AD mouse model, although not inducing decreased plaque burden, increased TTR protein concentration in the brain [105]. Nevertheless, resveratrol may protect via different mechanisms as it is reported that this polyphenol promotes intracellular degradation of Aβ via a mechanism that involves the proteasome, while not affecting the production of the peptide [106].…”

Transthyretin stability is critical in assisting beta amyloid clearance– Relevance of transthyretin stabilization in Alzheimer's disease

“…Resveratrol, another TTR stabilizer, a natural polyphenol found in grapes, berries, peanuts, and pomegranates, has been shown to reduce neurodegeneration and cognitive decline in mice displaying AD features . This compound was also described to lower the levels of secreted and intracellular Aβ peptides produced from different cell lines, to increase TTR levels and further decrease brain Aβ burden and to increase LRP1 levels in the treated AD animals . Moreover, resveratrol has been demonstrated to increase TTR affinity to Aβ .…”

“…45 This compound was also described to lower the levels of secreted and intracellular Aβ peptides produced from different cell lines, 46 to increase TTR levels 47 and further decrease brain Aβ burden and to increase LRP1 levels in the treated AD animals. 27 Moreover, resveratrol has been demonstrated to increase TTR affinity to Aβ. 25 However, the effect of TTR stabilization has never been specifically studied in Aβ transport and LRP1 levels.…”

“…One of such stabilizers, iododiflunisal (IDIF), when administrated to AD transgenic mice ameliorates AD features, such as cognitive function, brain Aβ deposition, and plasma Aβ levels . Moreover, oral administration of resveratrol, another TTR stabilizer present mainly in the grape skin, reduced significantly brain Aβ levels and amyloid deposits, increased LRP1 protein expression in both brain and liver of the AD mice, and increased TTR plasma levels …”

“…26 Moreover, oral administration of resveratrol, another TTR stabilizer present mainly in the grape skin, reduced significantly brain Aβ levels and amyloid deposits, increased LRP1 protein expression in both brain and liver of the AD mice, and increased TTR plasma levels. 27 Therefore, this study aimed to unravel the importance of TTR stability in Aβ clearance and LRP1 expression levels at the BBB and the liver, both by comparing the effects of human recombinant wild-type TTR (WT TTR) versus L55P TTR and by studying the impact of stabilizing L55P TTR using IDIF or resveratrol in this process.…”