Neuroprotective effects of the multitarget agent AVCRI104P3 in brain of middle-aged mice

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RECERCAT Home > Universitat de Barcelona > IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer > Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) > View document

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dc.contributor.author	Relat, Julia
dc.contributor.author	Come, Julio
dc.contributor.author	Perez, B.
dc.contributor.author	Camps García, Pelayo
dc.contributor.author	Muñoz-Torrero López-Ibarra, Diego
dc.contributor.author	Badia, Albert
dc.contributor.author	Giménez Llort, Lydia
dc.contributor.author	Clos, Victòria
dc.date	2019-01-29T15:18:14Z
dc.date	2019-01-29T15:18:14Z
dc.date	2018-09-04
dc.date	2019-01-29T15:18:14Z
dc.identifier	1661-6596
dc.identifier	681587
dc.identifier	30181440
dc.identifier.uri	http://hdl.handle.net/2445/127709
dc.description	Molecular factors involved in neuroprotection are key in the design of novelmultitarget drugs in aging and neurodegeneration. AVCRI104P3 is a huprine derivative that exhibits potent inhibitory effects on human AChE, BuChE, and BACE-1 activities, as well as on AChE-induced and self-induced Abeta aggregation. More recently, cognitive protection and anxiolytic-like effects have also been reported in mice treated with this compound. Now, we have assessed the ability of AVCRI104P3 (0.43 mg/kg, 21 days) to modulate the levels of some proteins involved in the anti-apoptotic/apoptotic processes (pAkt1, Bcl2, pGSK3beta, p25/p35), inflammation (GFAP and Iba1) and neurogenesis in C57BL/6 mice. The effects of AVCRI104P3 on AChE-R/AChE-S isoforms have been also determined. We have observed that chronic treatment of C57BL/6 male mice with AVCRI104P3 results in neuroprotective effects, increasing significantly the levels of pAkt1 and pGSK3beta in the hippocampus and Bcl2 in both hippocampus and cortex, but slightly decreasing synaptophysin levels. Astrogliosis and neurogenic markers GFAP and DCX remained unchanged after AVCRI104P3 treatment, whereas microgliosis was found to be significantly decreased pointing out the involvement of this compound in inflammatory processes. These results suggest that the neuroprotective mechanisms that are behind the cognitive and anxiolytic effects of AVCRI104P3 could be partly related to the potentiation of some anti-apoptotic and anti-inflammatory proteins and support the potential of AVCRI104P3 for the treatment of brain dysfunction associated with aging and/or dementia
dc.format	application/pdf
dc.language	eng
dc.publisher	MDPI
dc.relation	Reproducció del document publicat a: https://doi.org/10.3390/ijms19092615
dc.relation	International Journal of Molecular Sciences, 2018, vol. 19, num. 9, p. 2615
dc.relation	https://doi.org/10.3390/ijms19092615
dc.rights	cc-by (c) Relat, J. et al., 2018
dc.rights	http://creativecommons.org/licenses/by/3.0/es
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Apoptosi
dc.subject	Ratolins (Animals de laboratori)
dc.subject	Envelliment
dc.subject	Trastorns de la cognició
dc.subject	Apoptosis
dc.subject	Mice (Laboratory animals)
dc.subject	Population aging
dc.subject	Cognitive psychology
dc.title	Neuroprotective effects of the multitarget agent AVCRI104P3 in brain of middle-aged mice
dc.type	info:eu-repo/semantics/article
dc.type	info:eu-repo/semantics/publishedVersion

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