AZP2006, a new promising treatment for Alzheimer’s and related diseases

Abstract Progranulin (PGRN) is a protein with multiple functions including the regulation of neuroinflammation, neuronal survival, neurite and synapsis growth. Although the mechanisms of action of PGRN are currently unknown, its potential therapeutic application in treating neurodegenerative disease...

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Autores principales:	N. Callizot, C. Estrella, S. Burlet, A. Henriques, C. Brantis, M. Barrier, M. L. Campanari, P. Verwaerde
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/af022f0472c645e296c8b3fa2b7476bf
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spelling	oai:doaj.org-article:af022f0472c645e296c8b3fa2b7476bf2021-12-02T15:10:39ZAZP2006, a new promising treatment for Alzheimer’s and related diseases10.1038/s41598-021-94708-12045-2322https://doaj.org/article/af022f0472c645e296c8b3fa2b7476bf2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94708-1https://doaj.org/toc/2045-2322Abstract Progranulin (PGRN) is a protein with multiple functions including the regulation of neuroinflammation, neuronal survival, neurite and synapsis growth. Although the mechanisms of action of PGRN are currently unknown, its potential therapeutic application in treating neurodegenerative diseases is huge. Thus, strategies to increase PGRN levels in patients could provide an effective treatment. In the present study, we investigated the effects of AZP2006, a lysotropic molecule now in phase 2a clinical trial in Progressive Supranuclear Palsy patients, for its ability to increase PGRN level and promote neuroprotection. We showed for the first time the in vitro and in vivo neuroprotective effects of AZP2006 in neurons injured with Aβ1–42 and in two different pathological animal models of Alzheimer’s disease (AD) and aging. Thus, the chronic treatment with AZP2006 was shown to reduce the loss of central synapses and neurons but also to dramatically decrease the massive neuroinflammation associated with the animal pathology. A deeper investigation showed that the beneficial effects of AZP2006 were associated with PGRN production. Also, AZP2006 binds to PSAP (the cofactor of PGRN) and inhibits TLR9 receptors normally responsible for proinflammation when activated. Altogether, these results showed the high potential of AZP2006 as a new putative treatment for AD and related diseases.N. CallizotC. EstrellaS. BurletA. HenriquesC. BrantisM. BarrierM. L. CampanariP. VerwaerdeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q N. Callizot C. Estrella S. Burlet A. Henriques C. Brantis M. Barrier M. L. Campanari P. Verwaerde AZP2006, a new promising treatment for Alzheimer’s and related diseases
description	Abstract Progranulin (PGRN) is a protein with multiple functions including the regulation of neuroinflammation, neuronal survival, neurite and synapsis growth. Although the mechanisms of action of PGRN are currently unknown, its potential therapeutic application in treating neurodegenerative diseases is huge. Thus, strategies to increase PGRN levels in patients could provide an effective treatment. In the present study, we investigated the effects of AZP2006, a lysotropic molecule now in phase 2a clinical trial in Progressive Supranuclear Palsy patients, for its ability to increase PGRN level and promote neuroprotection. We showed for the first time the in vitro and in vivo neuroprotective effects of AZP2006 in neurons injured with Aβ1–42 and in two different pathological animal models of Alzheimer’s disease (AD) and aging. Thus, the chronic treatment with AZP2006 was shown to reduce the loss of central synapses and neurons but also to dramatically decrease the massive neuroinflammation associated with the animal pathology. A deeper investigation showed that the beneficial effects of AZP2006 were associated with PGRN production. Also, AZP2006 binds to PSAP (the cofactor of PGRN) and inhibits TLR9 receptors normally responsible for proinflammation when activated. Altogether, these results showed the high potential of AZP2006 as a new putative treatment for AD and related diseases.
format	article
author	N. Callizot C. Estrella S. Burlet A. Henriques C. Brantis M. Barrier M. L. Campanari P. Verwaerde
author_facet	N. Callizot C. Estrella S. Burlet A. Henriques C. Brantis M. Barrier M. L. Campanari P. Verwaerde
author_sort	N. Callizot
title	AZP2006, a new promising treatment for Alzheimer’s and related diseases
title_short	AZP2006, a new promising treatment for Alzheimer’s and related diseases
title_full	AZP2006, a new promising treatment for Alzheimer’s and related diseases
title_fullStr	AZP2006, a new promising treatment for Alzheimer’s and related diseases
title_full_unstemmed	AZP2006, a new promising treatment for Alzheimer’s and related diseases
title_sort	azp2006, a new promising treatment for alzheimer’s and related diseases
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/af022f0472c645e296c8b3fa2b7476bf
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AZP2006, a new promising treatment for Alzheimer’s and related diseases

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