Abstract
Physiologically, TTR is mainly acknowledged for being the plasma transporter of thyroxine (T4) and retinol. Under pathological conditions, several mutations in TTR are associated with familial amyloid polyneuropathy (FAP), a neurodegenerative disorder characterized by deposition of TTR amyloid fibrils, particularly in the peripheral nervous system (PNS), where it leads to axonal loss and neuronal death. Although it is well established that TTR synthesis occurs in the liver and in the choroid plexus (the sources of TTR in the plasma and cerebrospinal fluid –CSF, respectively), the origin of TTR deposited in the PNS of FAP patients is unknown. Under physiological conditions TTR has access to the nerve both through the blood and CSF. Additionally, a function for TTR in nerve biology could explain its preferential deposition, when mutated, in the PNS. In this respect, several studies using TTR knockout (KO) mice revealed new TTR functions specifically related to the nervous system: (1) the absence of TTR is associated with reduced signs of depressive-like behavior and with memory impairment; (2) TTR participates in sensorimotor performance; (3) TTR regulates neuropeptide maturation and, (4) TTR enhances nerve regeneration. In the following pages, these novel TTR functions related to the nervous system, as well as the use of TTR KO mice as a means to study them, will be discussed.
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Fleming, C.E., Nunes, A.F., Liz, M.A., Sousa, M.M. (2009). Transthyretin Null Mice as a Model to Study the Involvement of Transthyretin in Neurobiology: From Neuropeptide Processing to Nerve Regeneration. In: Richardson, S.J., Cody, V. (eds) Recent Advances in Transthyretin Evolution, Structure and Biological Functions. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00646-3_19
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