Proteomic alterations in the cerebellum and hippocampus in an Alzheimer's disease mouse model: alleviating effect of palmatine

Kiris, Irem and Kukula-Koch, Wirginia and Karayel-Basar, Merve and Gürel, Büşra and Coskun, Julide and Baykal, Ahmet Tarik (2023) Proteomic alterations in the cerebellum and hippocampus in an Alzheimer's disease mouse model: alleviating effect of palmatine. Biomedicine and Pharmacotherapy, 158 . ISSN 0753-3322 (Print) 1950-6007 (Online)

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Alzheimer's disease (AD) is one of the most prevalent diseases that lead to memory deficiencies, severe behavioral abnormalities, and ultimately death. The need for more appropriate treatment of AD continues, and remains a sought-after goal. Previous studies showed palmatine (PAL), an isoquinoline alkaloid, might have the potential for combating AD because of its in vitro and in vivo activities. In this study, we aimed to assess PAL's therapeutic potential and gain insights into the working mechanism on protein level in the AD mouse model brain, for the first time. To this end, PAL was administered to 12-month-old 5xFAD mice at two doses after its successful isolation from the Siberian barberry shrub. PAL (10 mg/kg) showed statistically significant improvement in the memory and learning phase on the Morris water maze test. The PAL's ability to pass through the blood-brain barrier was verified via Multiple Reaction Monitoring (MRM). Label-free proteomics analysis revealed PAL administration led to changes most prominently in the cerebellum, followed by the hippocampus, but none in the cortex. Most of the differentially expressed proteins in PAL compared to the 5xFAD control group (ALZ) were the opposite of those in ALZ in comparison to healthy Alzheimer's littermates (ALM) group. HS105, HS12A, and RL12 were detected as hub proteins in the cerebellum. Collectively, here we present PAL as a potential therapeutic candidate owing to its alleviating effect in 5xFAD mice on not only cognitive impairment but also proteomes in the cerebellum and hippocampus.
Item Type: Article
Uncontrolled Keywords: 5xFAD; Alzheimer's Disease; Label-free Proteomics; Neurodegeneration; Palmatine
Divisions: Sabancı University Nanotechnology Research and Application Center
Depositing User: Büşra Gürel
Date Deposited: 13 Apr 2023 11:58
Last Modified: 13 Apr 2023 11:58

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