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Neuroprotective effects of the multitarget agent AVCRI104P3 in brain of middle-aged mice
Relat, J. (Department of Pharmacology. Therapeutic and Toxicology. Autonomous University of Barcelona)
Come, J. (Department of Pharmacology. Therapeutic and Toxicology. Autonomous University of Barcelona)
Perez, B. (Department of Pharmacology. Therapeutic and Toxicology. Autonomous University of Barcelona)
Camps, P. (Laboratory of Pharmaceutical Chemistry (CSIC Associated Unit). Faculty of Pharmacy and Food Sciences. Institute of Biomedicine (IBUB). University of Barcelona)
Muñoz-Torrero, D. (Laboratory of Pharmaceutical Chemistry (CSIC Associated Unit). Faculty of Pharmacy and Food Sciences. Institute of Biomedicine (IBUB). University of Barcelona)
Badia Sancho, A. (Albert) (Department of Pharmacology. Therapeutic and Toxicology. Autonomous University of Barcelona)
Gimenez-Llort, L. (Department of Psychiatry and Forensic Medicine. Autonomous University of Barcelona)
Clos, M.V. (Department of Pharmacology. Therapeutic and Toxicology. Autonomous University of Barcelona)

Data: 2018
Resum: Molecular factors involved in neuroprotection are key in the design of novel multitarget 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 Aβ 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, pGSK3β, 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 pGSK3β 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.
Nota: Número d'acord de subvenció Generalitat de Catalunya/2017SGR106
Nota: Número d'acord de subvenció Generalitat de Catalunya/2014SGR52
Nota: Número d'acord de subvenció FEDER/SAF2017-82771-R
Nota: Número d'acord de subvenció FEDER/SAF2009-10553
Nota: Funding: Funding for this study was provided by the Ministerio de Ciencia, Innovación y Universidades, the Agencia Estatal de Investigación (AEI) and FEDER (SAF2009-10553, SAF2017-82771-R) and the Generalitat de Catalunya (2014SGR52, 2017SGR106).
Nota: MDPI-ACCESOBERT-UTP
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès.
Document: article ; recerca ; publishedVersion
Publicat a: International journal of molecular sciences, Vol. 19 Núm. 9 (april 2018) , p. 2615, ISSN 1422-0067

DOI: 10.3390/ijms19092615
PMID: 30181440


16 p, 3.1 MB

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