Shared cognitive and behavioral impairments in epilepsy and Alzheimer's disease and potential underlying mechanisms

Background: Alzheimer’s disease is one of the most common neurodegenerative diseases in many modern societies. The core pathogenesis of Alzheimer’s disease includes the aggregation of hyperphosphorylated Tau and abnormal Amyloid-β generation. In addition, previous studies have shown that neuroinflammation is one of the pathogenesis of Alzheimer’s disease. Formononetin, an isoflavone compound extracted from Trifolium pratense L., has been found to have various properties including anti-obesity, anti-inflammation, and neuroprotective effects. But there are very few studies on the treatment of Alzheimer’s disease with Formononetin. Objective: The present study focused on the protective activities of Formononetin on a high-fat dietinduced cognitive decline and explored the underlying mechanisms. Methods: Mice were fed with HFD for 10 weeks and intragastric administrated daily with metformin (300 mg/kg) and Formononetin (20 and 40 mg/kg). Results: We found that Formononetin (20, 40 mg/kg) significantly attenuated the learning and memory deficits companied by weight improvement and decreased the levels of blood glucose, total cholesterol and triglyceride in high-fat diet-induced mice. Meanwhile, we observed high-fat diet significantly caused the Tau hyperphosphorylation in the hippocampus of mice, whereas Formononetin reversed this effect. Additionally, Formononetin markedly reduced the levels of inflammation cytokines IL-1β and TNF-α in high-fat diet-induced mice. The mechanism study showed that Formononetin suppressed the pro-inflammatory NF-κB signaling and enhanced the anti-inflammatory Nrf-2/HO-1 signaling, which might be related to the regulation of PGC-1α in the hippocampus of high-fat diet -induced mice. Conclusion: Taken together, our results showed that Formononetin could improve the cognitive function by inhibiting neuroinflammation, which is attributed to the regulation of PGC-1α pathway in HFD-induced mice.

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Naringenin improves learning and memory in an Alzheimer's disease rat model: Insights into the underlying mechanisms

European Journal of Pharmacology ◽

10.1016/j.ejphar.2015.07.001 ◽

2015 ◽

Vol 764 ◽

pp. 195-201 ◽

Cited By ~ 49

Author(s):

Saeed Ghofrani ◽

Mohammad-Taghi Joghataei ◽

Simin Mohseni ◽

Tourandokht Baluchnejadmojarad ◽

Maryam Bagheri ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Learning And Memory ◽

Rat Model ◽

Underlying Mechanisms

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The influence of Schisandrin B on a model of Alzheimer’s disease using β-amyloid protein Aβ1-42-mediated damage in SH-SY5Y neuronal cell line and underlying mechanisms

Journal of Toxicology and Environmental Health Part A ◽

10.1080/15287394.2017.1367133 ◽

2017 ◽

Vol 80 (22) ◽

pp. 1199-1205 ◽

Cited By ~ 6

Author(s):

Ming Zhang ◽

Hong-xia Zheng ◽

Yang-yang Gao ◽

Bo Zheng ◽

Jing-ping Liu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cell Line ◽

Neuronal Cell ◽

Schisandrin B ◽

Amyloid Protein ◽

Neuronal Cell Line ◽

Model Of Alzheimer’S Disease ◽

Β Amyloid ◽

Underlying Mechanisms

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Trigonelline protects hippocampus against intracerebral Aβ(1–40) as a model of Alzheimer’s disease in the rat: insights into underlying mechanisms

Metabolic Brain Disease ◽

10.1007/s11011-018-0338-8 ◽

2018 ◽

Vol 34 (1) ◽

pp. 191-201 ◽

Cited By ~ 13

Author(s):

Javad Fahanik-Babaei ◽

Tourandokht Baluchnejadmojarad ◽

Farnaz Nikbakht ◽

Mehrdad Roghani

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Model Of Alzheimer’S Disease ◽

Underlying Mechanisms

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A Large-scale Comparison of Cortical and Subcortical Structural Segmentation Methods in Alzheimer’s Disease: a Statistical Approach

10.1101/2020.08.18.256321 ◽

2020 ◽

Author(s):

Jafar Zamani ◽

Ali Sadr ◽

Amir-Homayoun Javadi

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Large Scale ◽

Automated Segmentation ◽

Resonance Imaging ◽

Brain Areas ◽

Segmentation Methods ◽

Magnetic Resonance Imaging Mri ◽

Underlying Mechanisms ◽

The Brain

AbstractBackgroundAlzheimer’s disease (AD) is a neurodegenerative disease that leads to anatomical atrophy, as evidenced by magnetic resonance imaging (MRI). Automated segmentation methods are developed to help with the segmentation of different brain areas. However, their reliability has yet to be fully investigated. To have a more comprehensive understanding of the distribution of changes in AD, as well as investigating the reliability of different segmentation methods, in this study we compared volumes of cortical and subcortical brain segments, using automated segmentation methods in more than 60 areas between AD and healthy controls (HC).MethodsA total of 44 MRI images (22 AD and 22 HC, 50% females) were taken from the minimal interval resonance imaging in Alzheimer’s disease (MIRIAD) dataset. HIPS, volBrain, CAT and BrainSuite segmentation methods were used for the subfields of hippocampus, and the rest of the brain.ResultsWhile HIPS, volBrain and CAT showed strong conformity with the past literature, BrainSuite misclassified several brain areas. Additionally, the volume of the brain areas that successfully discriminated between AD and HC showed a correlation with mini mental state examination (MMSE) scores. The two methods of volBrain and CAT showed a very strong correlation. These two methods, however, did not correlate with BrainSuite.ConclusionOur results showed that automated segmentation methods HIPS, volBrain and CAT can be used in the classification of AD and HC. This is an indication that such methods can be used to inform researchers and clinicians of underlying mechanisms and progression of AD.

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Pathology, Risk Factors, and Oxidative Damage Related to Type 2 Diabetes-Mediated Alzheimer’s Disease and the Rescuing Effects of the Potent Antioxidant Anthocyanin

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/4051207 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Muhammad Sohail Khan ◽

Muhammad Ikram ◽

Tae Ju Park ◽

Myeong Ok Kim

Keyword(s):

Alzheimer’S Disease ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Alzheimer's Disease ◽

Inflammatory Cytokines ◽

Amyloid Beta ◽

Acid Oxidation ◽

Chronic Hyperglycemia ◽

Underlying Mechanisms

The pathology and neurodegeneration in type 2 diabetes- (T2D-) mediated Alzheimer’s disease (AD) have been reported in several studies. Despite the lack of information regarding the basic underlying mechanisms involved in the development of T2D-mediated AD, some common features of the two conditions have been reported, such as brain atrophy, reduced cerebral glucose metabolism, and insulin resistance. T2D phenotypes such as glucose dyshomeostasis, insulin resistance, impaired insulin signaling, and systemic inflammatory cytokines have been shown to be involved in the progression of AD pathology by increasing amyloid-beta accumulation, tau hyperphosphorylation, and overall neuroinflammation. Similarly, oxidative stress, mitochondrial dysfunction, and the generation of advanced glycation end products (AGEs) and their receptor (RAGE) as a result of chronic hyperglycemia may serve as critical links between diabetes and AD. The natural dietary polyflavonoid anthocyanin enhances insulin sensitivity, attenuates insulin resistance at the level of the target tissues, inhibits free fatty acid oxidation, and abrogates the release of peripheral inflammatory cytokines in obese (prediabetic) individuals, which are responsible for insulin resistance, systemic hyperglycemia, systemic inflammation, brain metabolism dyshomeostasis, amyloid-beta accumulation, and neuroinflammatory responses. In this review, we have shown that obesity may induce T2D-mediated AD and assessed the recent therapeutic advances, especially the use of anthocyanin, against T2D-mediated AD pathology. Taken together, the findings of current studies may help elucidate a new approach for the prevention and treatment of T2D-mediated AD by using the polyflavonoid anthocyanin.

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Catabolism of amyloid β peptide and pathogenesis of sporadic Alzheimer’s disease: towards understanding the underlying mechanisms

Alzheimer: 100 Years and Beyond - Research and Perspectives in Alzheimer’s Disease ◽

10.1007/978-3-540-37652-1_22 ◽

2006 ◽

pp. 201-206

Author(s):

Takaomi C. Saido

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Sporadic Alzheimer’S Disease ◽

Underlying Mechanisms

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Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau

Neuropsychopharmacology ◽

10.1038/s41386-020-00840-3 ◽

2020 ◽

Vol 46 (1) ◽

pp. 98-115 ◽

Cited By ~ 2

Author(s):

Sruti Rayaprolu ◽

Lenora Higginbotham ◽

Pritha Bagchi ◽

Caroline M. Watson ◽

Tian Zhang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Brain Network ◽

Protein Biomarkers ◽

Cellular Processes ◽

Complex Protein ◽

Underlying Mechanisms ◽

Novel Protein

AbstractThe repeated failures of amyloid-targeting therapies have challenged our narrow understanding of Alzheimer’s disease (AD) pathogenesis and inspired wide-ranging investigations into the underlying mechanisms of disease. Increasing evidence indicates that AD develops from an intricate web of biochemical and cellular processes that extend far beyond amyloid and tau accumulation. This growing recognition surrounding the diversity of AD pathophysiology underscores the need for holistic systems-based approaches to explore AD pathogenesis. Here we describe how network-based proteomics has emerged as a powerful tool and how its application to the AD brain has provided an informative framework for the complex protein pathophysiology underlying the disease. Furthermore, we outline how the AD brain network proteome can be leveraged to advance additional scientific and translational efforts, including the discovery of novel protein biomarkers of disease.

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Chiral gold nanoparticles enantioselectively rescue memory deficits in a mouse model of Alzheimer’s disease

Nature Communications ◽

10.1038/s41467-020-18525-2 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Ke Hou ◽

Jing Zhao ◽

Hui Wang ◽

Bin Li ◽

Kexin Li ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gold Nanoparticles ◽

Mouse Model ◽

Chiral Recognition ◽

Memory Deficits ◽

Aβ Peptides ◽

Promising Strategy ◽

Model Of Alzheimer’S Disease ◽

Behavioral Impairments

Abstract Preventing aggregation of amyloid beta (Aβ) peptides is a promising strategy for the treatment of Alzheimer’s disease (AD), and gold nanoparticles have previously been explored as a potential anti-Aβ therapeutics. Here we design and prepare 3.3 nm L- and D-glutathione stabilized gold nanoparticles (denoted as L3.3 and D3.3, respectively). Both chiral nanoparticles are able to inhibit aggregation of Aβ42 and cross the blood-brain barrier (BBB) following intravenous administration without noticeable toxicity. D3.3 possesses a larger binding affinity to Aβ42 and higher brain biodistribution compared with its enantiomer L3.3, giving rise to stronger inhibition of Aβ42 fibrillation and better rescue of behavioral impairments in AD model mice. This conjugation of a small nanoparticle with chiral recognition moiety provides a potential therapeutic approach for AD.

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