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Turkish Journal of Biology

Abstract

Background/aim: Alzheimer’s disease (AD), one of the most common health issues, is characterized by memory loss, severe behavioral disorders, and eventually death. Despite many studies, there are still no drugs that can treat AD or stop it from progressing. Previous in vitro tests showed that O-demethyl galantamine (ODG) might have a therapeutic potential owing to its 10 times higher acetylcholinesterase inhibitory activity than galantamine (GAL). Materials and methods: We aimed to assess effect of ODG on a molecular level 12-month-old 5xFAD Alzheimer’s mouse model. To this end, following the administrations of ODG and GAL, used as a positive control, protein alterations were investigated in the brain’s cortex, hippocampus, and cerebellum regions. Surprisingly, GAL altered proteins prominently in the cortex, while ODG exclusively exerted its effect on the cerebellum. Results: GNB1, GNB2, NDUFS6, PAK2, and RhoA proteins were identified as the top 5 hub proteins in the cerebellum of ODG treated mice. Re-regulation of these proteins through Ras signaling and retrograde endocannabinoid signaling pathways that were found to be enriched, might contribute to reversing AD-induced molecular changes.Conclusion: We suggest that, since it aims specifically the cerebellum, ODG may be further evaluated for combination therapies for AD.

Author ORCID Identifier

İREM KIRIŞ: 0000-0003-0963-378X

MERVE KARAYEL BAŞAR: 0000-0001-6460-4151

BÜŞRA Gurel: 0000-0001-9779-1467

TOMASZ MROCZEK: 0000-0002-5267-7182

AHMET BAYKAL: 0000-0002-8814-7351

DOI

10.55730/1300-0152.2692

Keywords

5xFAD, Alzheimer's disease, Label-free Proteomics, Neurodegeneration, O-demethyl galantamine, Sanguinine

First Page

163

Last Page

173

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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