The identification of effective pharmacological tools for Alzheimer’s disease (AD) represents one of the main challenges for therapeutic discovery. Due to the variety of pathological processes associated with AD, a promising route for pharmacological intervention involves the development of new chemical entities that can restore cellular homeostasis. To investigate this strategy, we designed and synthetized SG2, a compound related to the thyroid hormone thyroxine, that shares a pleiotropic activity with its endogenous parent compound, including autophagic flux promotion, neuroprotection, and metabolic reprogramming. We demonstrate herein that SG2 acts in a pleiotropic manner to induce recovery in a C. elegans model of AD based on the overexpression of Aβ42 and improves learning abilities in the 5XFAD mouse model of AD. Further, in vitro ADME-Tox profiling and toxicological studies in zebrafish confirmed the low toxicity of this compound, which represents a chemical starting point for AD drug development.
Identification of a Thyroid Hormone Derivative as a Pleiotropic Agent for the Treatment of Alzheimer’s Disease / Runfola, M.; Perni, M.; Yang, X.; Marchese, M.; Bacci, A.; Mero, S.; Santorelli, F. M.; Polini, B.; Chiellini, G.; Giuliani, D.; Vilella, A.; Bodria, M.; Daini, E.; Vandini, E.; Rudge, S.; Gul, S.; Wakelam, M. O. J.; Vendruscolo, M.; Rapposelli, S.. - In: PHARMACEUTICALS. - ISSN 1424-8247. - 14:12(2021), pp. 1330-1337. [10.3390/ph14121330]
Data di pubblicazione: | 2021 | |
Titolo: | Identification of a Thyroid Hormone Derivative as a Pleiotropic Agent for the Treatment of Alzheimer’s Disease | |
Autore/i: | Runfola, M.; Perni, M.; Yang, X.; Marchese, M.; Bacci, A.; Mero, S.; Santorelli, F. M.; Polini, B.; Chiellini, G.; Giuliani, D.; Vilella, A.; Bodria, M.; Daini, E.; Vandini, E.; Rudge, S.; Gul, S.; Wakelam, M. O. J.; Vendruscolo, M.; Rapposelli, S. | |
Autore/i UNIMORE: | ||
Digital Object Identifier (DOI): | http://dx.doi.org/10.3390/ph14121330 | |
Rivista: | ||
Volume: | 14 | |
Fascicolo: | 12 | |
Pagina iniziale: | 1330 | |
Pagina finale: | 1337 | |
Codice identificativo ISI: | WOS:000736890700001 | |
Codice identificativo Scopus: | 2-s2.0-85122733556 | |
Codice identificativo Pubmed: | 34959730 | |
Citazione: | Identification of a Thyroid Hormone Derivative as a Pleiotropic Agent for the Treatment of Alzheimer’s Disease / Runfola, M.; Perni, M.; Yang, X.; Marchese, M.; Bacci, A.; Mero, S.; Santorelli, F. M.; Polini, B.; Chiellini, G.; Giuliani, D.; Vilella, A.; Bodria, M.; Daini, E.; Vandini, E.; Rudge, S.; Gul, S.; Wakelam, M. O. J.; Vendruscolo, M.; Rapposelli, S.. - In: PHARMACEUTICALS. - ISSN 1424-8247. - 14:12(2021), pp. 1330-1337. [10.3390/ph14121330] | |
Tipologia | Articolo su rivista |
File in questo prodotto:
File | Descrizione | Tipologia | |
---|---|---|---|
pharmaceuticals SG2-14-01330.pdf | ARTICOLO PRINCIPALE | Versione dell'editore (versione pubblicata) | Open Access Visualizza/Apri |
Pubblicazioni consigliate

I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris