Triggering neuroprotective pathways to prevent neurodegeneration: role of estrogen receptor beta/neuroglobin signaling in Huntington disease

Coordinatore: Prof.ssa Maria Marino P.I. - Unità di Pisa Prof.ssa Elisabetta Orlandini, Prof.ssa Susanna Nencetti

Ente finanziatore: PRIN – Bando 2017 Prot. 2017SNRXH3

Budget: 932 000 €.

Partners: Università degli Studi Roma Tre, Università degli Studi di Roma "La Sapienza", Università degli Studi del Piemonte Orientale, Università degli Studi di Napoli Federico II, Università degli Studi di Roma "Tor Vergata"

Durata: agosto 2019 - febbraio 2023

Curative treatments of the neurodegenerative diseases including Huntington disease (HD) are lacking or inefficient being only symptomatic. To discover and develop interventions to delay the onset of HD, as well as other neurodegenerative diseases, is mandatory . Here, we propose to restore the neuroglobin-estrogen receptor beta (NGB-ERbeta) neuroprotective pathway as a novel approach to develop interventions to delay and/or prevent the onset of HD. Our preliminary datademonstrated that ligands of ERbeta enhance NGB levels and facilitate neuron survival both on cells and on in vivo models of HD. On these preliminary data, this proposal aims to discover new compounds more efficient to up-regulate NGB levels in neurons and to maintain its protective role in alleviating the symptoms and slowing down the progress of HD. To reach this aim, this proposal is devoted to the discovery of novel NGB inducers originating from natural compounds and synthetic small molecules libraries to define their impact on in vivo and in vitro HD models.