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Int. J. Mol. Sci. 2018, 19(9), 2615; https://doi.org/10.3390/ijms19092615

Neuroprotective Effects of the Multitarget Agent AVCRI104P3 in Brain of Middle-Aged Mice

1
Neuroscience Institute, Autonomous University of Barcelona, 08193 Barcelona, Spain
2
Department of Pharmacology, Therapeutic and Toxicology, Autonomous University of Barcelona, 08193 Barcelona, Spain
3
Laboratory of Pharmaceutical Chemistry (CSIC Associated Unit), Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain
4
Department of Psychiatry and Forensic Medicine, Autonomous University of Barcelona, 08193 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Received: 1 August 2018 / Revised: 14 August 2018 / Accepted: 15 August 2018 / Published: 4 September 2018
(This article belongs to the Special Issue Neuroprotective Strategies 2018)
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Abstract

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. View Full-Text
Keywords: acetylcholinesterase inhibitors; huprine derivatives; AVCRI104P3; apoptosis; neuroprotection; neuroinflammation acetylcholinesterase inhibitors; huprine derivatives; AVCRI104P3; apoptosis; neuroprotection; neuroinflammation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Relat, J.; Come, J.; Perez, B.; Camps, P.; Muñoz-Torrero, D.; Badia, A.; Gimenez-Llort, L.; Clos, M.V. Neuroprotective Effects of the Multitarget Agent AVCRI104P3 in Brain of Middle-Aged Mice. Int. J. Mol. Sci. 2018, 19, 2615.

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