Cinnamaldehyde Regulates Insulin and Caspase-3 Signaling Pathways in the Sporadic Alzheimer’s Disease Model: Involvement of Hippocampal Function via IRS-1, Akt, and GSK-3β Phosphorylation

Bagheri‐Mohammadi, Saeid; Askari, Sahar; Alani, Behrang; Moosavi, Maryam; Ghasemi, Rasoul

doi:10.1007/s12031-022-02075-x

Cited by 8 publications

(6 citation statements)

References 46 publications

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“…Beta boswellic acid, a primary component of the Boswellia serrata plant, exhibits a protective effect against streptozotocin-induced sporadic AD by reducing tau hyperphosphorylation, increasing reelin levels, and enhancing learning and memory in rats [ 99 ]. Cinnamaldehyde (Cin), a primary compound of cinnamon, ameliorated recognition/spatial memory impairments and anxiety-like behavior, reversed STZ-induced effects on AB aggregation and caspase-3 cleavage in the hippocampus, and regulated hippocampal IRS-1/AKT/GSK-33 phosphorylation in a model of sporadic Alzheimer’s disease [ 100 ]. Pioglitazone, a PPARγ agonist, can decrease β Amyloid levels in a neuronal model of AD by suppressing PPARγ phosphorylation and reducing CDK5 expression [ 101 ].…”

Section: Treatment Strategy Based On Pptmsmentioning

confidence: 99%

Abnormal protein post-translational modifications induces aggregation and abnormal deposition of protein, mediating neurodegenerative diseases

Li,

Wang

et al. 2024

Cell Biosci

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Protein post-translational modifications (PPTMs) refer to a series of chemical modifications that occur after the synthesis of protein. Proteins undergo different modifications such as phosphorylation, acetylation, ubiquitination, and so on. These modifications can alter the protein’s structure, function, and interaction, thereby regulating its biological activity. In neurodegenerative diseases, several proteins undergo abnormal post-translational modifications, which leads to aggregation and abnormal deposition of protein, thus resulting in neuronal death and related diseases. For example, the main pathological features of Alzheimer’s disease are the aggregation of beta-amyloid protein and abnormal phosphorylation of tau protein. The abnormal ubiquitination and loss of α-synuclein are related to the onset of Parkinson’s disease. Other neurodegenerative diseases such as Huntington’s disease, amyotrophic lateral sclerosis, and so on are also connected with abnormal PPTMs. Therefore, studying the abnormal PPTMs in neurodegenerative diseases is critical for understanding the mechanism of these diseases and the development of significant therapeutic strategies. This work reviews the implications of PPTMs in neurodegenerative diseases and discusses the relevant therapeutic strategies.

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Section: Treatment Strategy Based On Pptmsmentioning

confidence: 99%

Abnormal protein post-translational modifications induces aggregation and abnormal deposition of protein, mediating neurodegenerative diseases

Li,

Wang

et al. 2024

Cell Biosci

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“…Caspase-3 (CASP3), a cytoplasmic protease, plays a crucial role in apoptosis [58]. Research has shown that CASP3 is involved in the cleavage of β-amyloid protein, as well as Tau protein and presenilin protein (PS1, PS2), which are closely associated with AD [59].…”

Section: Molecular Dynamics Simulation Of the Casp3-6-gingerol Complexmentioning

confidence: 99%

Screening of Active Substances Regulating Alzheimer’s Disease in Ginger and Visualization of the Effectiveness on 6-Gingerol Pathway Targets

Pan,

Li,

Zhao

et al. 2024

Foods

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Ginger has been reported to potentially treat Alzheimer’s disease (AD), but the specific compounds responsible for this biological function and their mechanisms are still unknown. In this study, a combination of network pharmacology, molecular docking, and dynamic simulation technology was used to screen active substances that regulate AD and explore their mechanisms. The TCMSP, GeneCards, OMIM, and DisGeNET databases were utilized to obtain 95 cross-targets related to ginger’s active ingredients and AD as key targets. A functional enrichment analysis revealed that the pathways in which ginger’s active substances may be involved in regulating AD include response to exogenous stimuli, response to oxidative stress, response to toxic substances, and lipid metabolism, among others. Furthermore, a drug-active ingredient–key target interaction network diagram was constructed, highlighting that 6-Gingerol is associated with 16 key targets. Additionally, a protein–protein interaction (PPI) network was mapped for the key targets, and HUB genes (ALB, ACTB, GAPDH, CASP3, and CAT) were identified. Based on the results of network pharmacology and cell experiments, 6-Gingerol was selected as the active ingredient for further investigation. Molecular docking was performed between 6-Gingerol and its 16 key targets, and the top three proteins with the strongest binding affinities (ACHE, MMP2, and PTGS2) were chosen for molecular dynamics analysis together with the CASP3 protein as the HUB gene. The findings indicate that 6-Gingerol exhibits strong binding ability to these disease targets, suggesting its potential role in regulating AD at the molecular level, as well as in abnormal cholinesterase metabolism and cell apoptosis, among other related regulatory pathways. These results provide a solid theoretical foundation for future in vitro experiments using actual cells and animal experiments to further investigate the application of 6-Gingerol.

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“…Numerous mitochondrial functions have been detected that can influence AD states. These include reduced glucose metabolism, mitochondrial enzymatic impairment, and elevated ROS production [before the formation of amyloid‐beta (Aβ) and tau tangles] 82,88 . Besides, some aspects of mitochondrial dynamics are dysfunction in the early stage of AD 89,90 such as an insult in the balance between mitochondrial fusion and fission, representing the mitochondrial dividing and also binding with one another, reduced mitochondrial axonal transport process, decreased the percentage of mitochondria in the cell, and alter in organelle size, with mitochondria in AD conditions maintaining much shorter and wider shapes 82 .…”

Section: Mitochondrial Biochemical and Dynamic Alterations In Admentioning

confidence: 99%

“…These include reduced glucose metabolism, mitochondrial enzymatic impairment, and elevated ROS production [before the formation of amyloidbeta (Aβ) and tau tangles]. 82,88 Besides, some aspects of mitochondrial dynamics are dysfunction in the early stage of AD 89,90 such as an insult in the balance between mitochondrial fusion and fission, representing the mitochondrial dividing and also binding with one another, reduced mitochondrial axonal transport process, decreased the percentage of mitochondria in the cell, and alter in organelle size, with mitochondria in AD conditions maintaining much shorter and wider shapes. 82 Importantly, AD-related impairments lead to neuronal cell Ca 2+ ions influx and elevated ROS generation results in the activation of downstream proteases (calpain) and also protein kinase that acts on organelle fission/fusion GTPases (mitochondria) and alters mitochondrial fusion and fission in pathological states.…”

Section: Mitochondrial Biochemical and Dynamic Alterations In Admentioning

confidence: 99%

The mitochondrial calcium signaling, regulation, and cellular functions: A novel target for therapeutic medicine in neurological disorders

Bagheri‐Mohammadi

Farjami

Suha

et al. 2023

J of Cellular Biochemistry

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Mitochondrial calcium (Ca 2+ ) dynamics play critical roles in regulating vital physiological conditions in the brain. Importantly, Mitochondria-associated endoplasmic reticulum (ER) membranes serve different cellular functions including Ca 2+ signaling, bioenergetics, phospholipid biosynthesis, cholesterol esterification, programmed cell death, and communication between the two organelles. Several Ca 2+ -transport systems specialize at the mitochondria, ER, and their contact sites that provide tight control of mitochondrial Ca 2+ signaling at the molecular level. The biological function of Ca 2+ channels and transporters as well as the role of mitochondrial Ca 2+ signaling in cellular homeostasis can open new perspectives for investigation and molecular intervention. Emerging evidence suggests that abnormalities in ER/mitochondrial brain functions and dysregulation of Ca 2+ homeostasis are neuropathological hallmarks of neurological disorders like Alzheimer's disease, but little evidence is available to demonstrate their relationship to disease pathogenesis and therapeutic approaches. In recent years, the detection of the molecular mechanism regulating cellular Ca 2+ homeostasis and also mitochondrial functions have expanded the number of targeted treatments.The main experimental data identify beneficial effects, whereas some scientific trials did not meet the expectations. Together with an overview of the important function of mitochondria, this review paper introduced the possible tested therapeutic approaches that target mitochondria in the context of neurodegenerative diseases. Since these treatments in neurological disorders have shown different degrees of progress, it is essential to perform a detailed assessment of the significance of mitochondrial deterioration in neurodegenerative diseases and of a pharmacological treatment at this stage.

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Cinnamaldehyde Regulates Insulin and Caspase-3 Signaling Pathways in the Sporadic Alzheimer’s Disease Model: Involvement of Hippocampal Function via IRS-1, Akt, and GSK-3β Phosphorylation

Cited by 8 publications

References 46 publications

Abnormal protein post-translational modifications induces aggregation and abnormal deposition of protein, mediating neurodegenerative diseases

Abnormal protein post-translational modifications induces aggregation and abnormal deposition of protein, mediating neurodegenerative diseases

Screening of Active Substances Regulating Alzheimer’s Disease in Ginger and Visualization of the Effectiveness on 6-Gingerol Pathway Targets

The mitochondrial calcium signaling, regulation, and cellular functions: A novel target for therapeutic medicine in neurological disorders

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