Transthyretin: more than meets the eye.

Transthyretin (TTR) is a plasma protein mostly known for being the transporter of thyroxine and retinol. When mutated, TTR is also well-described as the cause of familial amyloid polyneuropathy, a neurodegenerative lethal disorder characterized by systemic deposition of TTR amyloid fibrils, particularly in the peripheral nervous system. Recent studies have determined that besides its carrier properties, TTR is an important protein in peripheral and central nervous system physiology, namely by participating in behavior, in the maintenance of normal cognitive processes during ageing, amidated neuropeptide processing and nerve regeneration. Additionally, it has been proposed that TTR is neuroprotective in Alzheimer's disease, by preventing the formation of amyloid beta fibrils. With the advent of powerful screening techniques, TTR has also been linked to a number of other pathological conditions, including Parkinson's disease, schizophrenia, depression, among others. These associations, together with the recently unraveled nervous system-related functions, suggest that the relevance of TTR in physiology, particularly in neurobiology, is undervalued and that additional research in this field is needed. The aim of this review is to integrate in a critical perspective the current scattered knowledge concerning TTR most and less acknowledged functions and its association with several neuropathologies.