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Transthyretin: the servant of many masters

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Abstract

Transthyretin (TTR) (formerly, thyroxine binding prealbumin) is an evolutionarily conserved serum and cerebrospinal fluid protein that transports holo-retinol-binding protein and thyroxine. Its serum concentration has been widely used to assess clinical nutritional status. It is also well known that wild-type transthyretin and approximately 100 different mutants give rise to a variety of forms of systemic amyloid deposition. It has been suspected and recently established that TTR can suppress the Alzheimer’s disease phenotype in transgenic animal models of cerebral Aβ deposition. Thus, while TTR is a systemic amyloid precursor, in the brain it seems to have an anti-amyloidogenic effect. TTR is found in other organs as a result of local synthesis or transport, suggesting that it may have other, as yet undiscovered, functions. It is possible that its capacity to bind many classes of compounds allows it to serve as an endogenous detoxifier of molecules with potential pathologic effects.

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Acknowledgements

This work was supported by National Institute on Aging Grants R01 AG30027 (to J.N.B.) and R01 AG19259 (to J.N.B.), the W. M. Keck Foundation (to J.N.B.) and The American Heart Association BGIA award 0865061F (to N.R.).

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Correspondence to Joel N. Buxbaum.

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Buxbaum, J.N., Reixach, N. Transthyretin: the servant of many masters. Cell. Mol. Life Sci. 66, 3095–3101 (2009). https://doi.org/10.1007/s00018-009-0109-0

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