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Adv Pharm Bull. 2020;10(3): 452-457.
doi: 10.34172/apb.2020.055
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  PDF Download: 36

Research Article

Contribution of Lysosome and Sigma Receptors to Neuroprotective Effects of Memantine Against Beta-Amyloid in the SH-SY5Y Cells

Mojtaba Keshavarz 1 * ORCID logo, Majid Reza Farrokhi 1 ORCID logo, Elahe Amirinezhad Fard 1 ORCID logo, Mohammad Mehdipour 2 ORCID logo

1 Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
2 Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.

Abstract

Purpose: Memantine is an approved drug for the treatment of Alzheimer’s disease (AD). Autophagy,lysosome dysfunction, and sigma receptors have possible roles in the pathophysiology of AD.Therefore, we aimed to investigate the contribution of sigma receptors and lysosome inhibitionto the neuroprotective effects of memantine against amyloid-beta (Aβ)-induced neurotoxicity inSH-SY5Y cells.Methods: We determined the neuroprotective effects of memantine (2.5 μM), dizocilpine(MK801, as a selective N-methyl-D-aspartate (NMDA) receptor antagonist) (5 μM) against Aβ25–35 (2 μg/μL)-induced neurotoxicity. We used chloroquine (10, 20, and 40 μM) as a lysosomeinhibitor and BD-1063 (1, 10, and 30 μM) as a selective sigma receptor antagonist. The MTTassay was used to measure the neurotoxicity in the SH-SY5Y cells. Data were analyzed usingthe one-way ANOVA.Results: Memantine (2.5 μM), dizocilpine (5 μM), chloroquine (10 and 20 μM) and BD-1063(1, 10 and 30 μM) decreased the neurotoxic effects of Aβ on the SH-SY5Y cells. However,chloroquine (40 μM) increased the neurotoxic effects of Aβ. Cell viability in the cells treatedwith memantine + Aβ + chloroquine (10, 20, and 40 μM) was significantly lower than thememantine + Aβ-treated group. Moreover, cell viability in the memantine + Aβ group washigher than the memantine + Aβ + BD-1063 (10 and 30 μM) groups.Conclusion: The lysosomal and sigma receptors may contribute to the neuroprotectivemechanism of memantine and other NMDA receptor antagonists. Moreover, the restoration oflysosomes function and the modulation of sigma receptors are potential targets in the treatmentof AD.
Keywords: Amyloid beta-Peptides, Lysosomes, Memantine, Neuroprotection, Sigma receptors
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Submitted: 26 Sep 2018
Revision: 27 Aug 2019
Accepted: 14 Nov 2019
ePublished: 11 May 2020
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