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

Kiris, Irem; Kukuła-Koch, Wirginia; Karayel-Basar, Merve; Gürel, Büşra; Coskun, Julide; Baykal, Ahmet

doi:10.1016/j.biopha.2022.114111

Cited by 18 publications

(7 citation statements)

References 95 publications

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“…The effects of palmatine on the nervous system have received widespread attention in recent years. Palmatine could pass the blood-brain barrier, improve cognitive impairment in 5xFAD mice after intraperitoneal injection, and alleviate the cerebellum and hippocampus proteome ( Kiris et al, 2023 ). The administration of palmatine could effectively decrease the levels of pro-inflammatory cytokines and increase the levels of anti-inflammatory cytokines in LPS-induced BV2 cells ( Wang et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Screening and evaluation of metabolites binding PRAS40 from Erxian decoction used to treat spinal cord injury

Lin,

Yan,

Sun

et al. 2024

Front. Pharmacol.

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Objective: The PRAS40 is an essential inhibitory subunit of the mTORC1 complex, which regulates autophagy. It has been suggested that Erxian Decoction (EXD) could treat spinal cord injury (SCI) via the autophagy pathway. However, the mechanism of whether EXD acts through PRAS40 remains unclear.Methods: With the help of immobilized PRAS40, isothermal titration calorimetry (ITC) and molecular docking, the bioactive metabolites in the EXD were screened. To establish in vitro SCI models, PC12 cells were exposed to hydrogen peroxide (H2O2) and then treated with the identified EXD substances. Furthermore, Western blot assay was carried out to identify potential molecular mechanisms involved. For assessing the effect of metabolites in vivo, the SCI model rats were first pretreated with or without the metabolite and then subjected to the immunohistochemistry (IHC) staining, Basso, Beattie & Bresnahan (BBB) locomotor rating scale, and H&E staining.Results: The immobilized PRAS40 isolated indole, 4-nitrophenol, terephthalic acid, palmatine, sinapinaldehyde, and 3-chloroaniline as the potential ligands binding to PRAS40. Furthermore, the association constants of palmatine and indole as 2.84 × 106 M-1 and 3.82 × 105 M-1 were elucidated via ITC due to the drug-like properties of these two metabolites. Molecular docking results also further demonstrated the mechanism of palmatine binding to PRAS40. Western blot analysis of PC12 cells demonstrated that palmatine inhibited the expression of p-mTOR by binding to PRAS40, activating the autophagic flux by markedly increasing LC3. The injection of palmatine (10μM and 20 μM) indicated notably increased BBB scores in the SCI rat model. Additionally, a dose-dependent increase in LC3 was observed by IHC staining.Conclusion: This research proved that EXD comprises PRAS40 antagonists, and the identified metabolite, palmatine, could potentially treat SCI by activating the autophagic flux.

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Section: Discussionmentioning

confidence: 99%

Screening and evaluation of metabolites binding PRAS40 from Erxian decoction used to treat spinal cord injury

Lin,

Yan,

Sun

et al. 2024

Front. Pharmacol.

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“…The membranes were washed and exposed with Clarity Western ECL Substrate (Bio‐Rad), and the chemiluminescence signal was acquired using ChemiDoc MP Imaging System (Bio‐Rad). The total protein loaded in each lane was calculated as a normalisation/loading control, and total protein normalisation analysis was performed using ImageLab Software Version 6.1 (Bio‐Rad) (Kiris et al, 2023).…”

Section: Methodsmentioning

confidence: 99%

“…How to cite this article: Karayel-Basar, M., Uras, I., Kiris, I., & Baykal, A. T. (2023). Detection of proteomic alterations at different stages in a Huntington's disease mouse model via matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging.…”

Section: Data Availability Statementmentioning

confidence: 99%

Detection of proteomic alterations at different stages in a Huntington's disease mouse model via matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) imaging

Karayel-Basar

Uras

Kiris

et al. 2023

Eur J of Neuroscience

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Huntington's disease (HD) is a progressive and irreversible neurodegenerative disease leading to the inability to carry out daily activities and for which no cure exists. The underlying mechanisms of the disease have not been fully elucidated yet. Matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI) allows the spatial information of proteins to be obtained upon the tissue sections without homogenisation. In this study, we aimed to examine proteomic alterations in the brain tissue of an HD mouse model with MALDI‐MSI coupled to LC–MS/MS system. We used 3‐, 6‐ and 12‐month‐old YAC128 mice representing pre‐stage, mild stage and pathological stage of the HD and their non‐transgenic littermates, respectively. The intensity levels of 89 proteins were found to be significantly different in YAC128 in comparison to their control mice in the pre‐stage, 83 proteins in the mild stage, and 82 proteins in the pathological stage. Among them, Tau, EF2, HSP70, and NogoA proteins were validated with western blot analysis. In conclusion, the results of this study have provided remarkable new information about the spatial proteomic alterations in the HD mouse model, and we suggest that MALDI‐MSI is an excellent technique for identifying such regional proteomic changes and could offer new perspectives in examining complex diseases.

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“…Analyses of both on-tissue and tissue section lysates' tryptic peptides and their data processing were done according to our previous studies. 68 Briefly, LC-MS/MS experiments were performed using a nanoACQUITY UPLC coupled to a SYNAPT G2-Si HDMS system (Waters Corp., Milford, MA, USA). The columns were equilibrated with…”

Section: Lc-ms/ms Analysismentioning

confidence: 99%

Detection of early proteomic alterations in 5xFAD Alzheimer's disease neonatal mouse model via MALDI‐MSI

Uras

Karayel-Basar

Sahin

et al. 2023

Alzheimer's & Dementia

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Alzheimer's disease (AD) is a debilitating neurodegenerative disorder, characterized by memory deficit and dementia. AD is considered a multifactorial disorder where multiple processes like amyloid‐beta and tau accumulation, axonal degeneration, synaptic plasticity, and autophagic processes plays an important role. In this study, the spatial proteomic differences in the neonatal 5xFAD brain tissue were investigated using MALDI‐MSI coupled to LC‐MS/MS, and the statistically significantly altered proteins were associated with AD. Thirty‐five differentially expressed proteins (DEPs) between the brain tissues of neonatal 5xFAD and their littermate mice were detected via MALDI‐MSI technique. Among the 35 proteins identified, 26 of them were directly associated with AD. Our results indicated a remarkable resemblance in the protein expression profiles of neonatal 5xFAD brain when compared to AD patient specimens or AD mouse models. These findings showed that the molecular alterations in the AD brain existed even at birth and that some proteins are neurodegenerative presages in neonatal AD brain.Highlights Spatial proteomic alterations in the 5xFAD mouse brain compared to the littermate. 26 out of 35 differentially expressed proteins associated with Alzheimer's disease (AD). Molecular alterations and neurodegenerative presages in neonatal AD brain. Alterations in the synaptic function an early and common neurobiological thread.

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

Cited by 18 publications

References 95 publications

Screening and evaluation of metabolites binding PRAS40 from Erxian decoction used to treat spinal cord injury

Screening and evaluation of metabolites binding PRAS40 from Erxian decoction used to treat spinal cord injury

Detection of proteomic alterations at different stages in a Huntington's disease mouse model via matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) imaging

Detection of early proteomic alterations in 5xFAD Alzheimer's disease neonatal mouse model via MALDI‐MSI

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