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Transthyretin Stabilization: An Emerging Strategy for the Treatment of Alzheimer’s Disease?

Title
Transthyretin Stabilization: An Emerging Strategy for the Treatment of Alzheimer’s Disease?
Authors
Saponaro, FedericaKim, Jin HaeChiellini, Grazia
DGIST Authors
Kim, Jin Hae
Issue Date
2020-11
Citation
International Journal of Molecular Sciences, 21(22), 8672
Type
Article
Article Type
Review
Author Keywords
transthyretinprotein misfoldingprotein aggregationamyloidosisAlzheimer&#8217s diseaseTTR stabilizers
Keywords
RETINOL-BINDING-PROTEINFAMILIAL AMYLOID POLYNEUROPATHYCEREBROSPINAL-FLUIDBETA PEPTIDETHYROXINE-BINDINGCHOROID-PLEXUSNATIVE-STATEMOUSE MODELVITAMIN-APREALBUMIN
ISSN
1661-6596
Abstract
Transthyretin (TTR), previously named prealbumin is a plasma protein secreted mainly by the liver and choroid plexus (CP) that is a carrier for thyroid hormones (THs) and retinol (vitamin A). The structure of TTR, with four monomers rich in β-chains in a globular tetrameric protein, accounts for the predisposition of the protein to aggregate in fibrils, leading to a rare and severe disease, namely transthyretin amyloidosis (ATTR). Much effort has been made and still is required to find new therapeutic compounds that can stabilize TTR (“kinetic stabilization”) and prevent the amyloid genetic process. Moreover, TTR is an interesting therapeutic target for neurodegenerative diseases due to its recognized neuroprotective properties in the cognitive impairment context and interestingly in Alzheimer’s disease (AD). Much evidence has been collected regarding the neuroprotective effects in AD, including through in vitro and in vivo studies as well as a wide range of clinical series. Despite this supported hypothesis of neuroprotection for TTR, the mechanisms are still not completely clear. The aim of this review is to highlight the most relevant findings on the neuroprotective role of TTR, and to summarize the recent progress on the development of TTR tetramer stabilizers. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
URI
http://hdl.handle.net/20.500.11750/12709
DOI
10.3390/ijms21228672
Publisher
MDPI AG
Related Researcher
Files:
Collection:
Department of New BiologyProtein Structure Aging Laboratory1. Journal Articles


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