A Potential New Mechanism Linking Type II Diabetes Mellitus and Alzheimer's Disease

Adam, Alejandro P.

doi:10.1002/bies.201800061

Cited by 4 publications

(3 citation statements)

References 7 publications

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“…Furthermore, the activation of JNK pathways (a subtype of the MAPK pathway) can inhibit PI3K signaling and lead to IR. Increased intracellular Ca 2+ has been proposed as a possible mechanism that affects the localization and protein–protein interactions of key signaling mediators, explaining both JNK activation and the inhibition of PI3K signaling [ 39 ].…”

Section: Metabolic Syndrome and Alzheimer’s Diseasementioning

confidence: 99%

Metabolic Profile of Alzheimer’s Disease: Is 10-Hydroxy-2-decenoic Acid a Pertinent Metabolic Adjuster?

Gong,

Luo,

et al. 2023

Metabolites

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Alzheimer’s disease (AD) represents a significant public health concern in modern society. Metabolic syndrome (MetS), which includes diabetes mellitus (DM) and obesity, represents a modifiable risk factor for AD. MetS and AD are interconnected through various mechanisms, such as mitochondrial dysfunction, oxidative stress, insulin resistance (IR), vascular impairment, inflammation, and endoplasmic reticulum (ER) stress. Therefore, it is necessary to seek a multi-targeted and safer approach to intervention. Thus, 10-hydroxy-2-decenoic acid (10-HDA), a unique hydroxy fatty acid in royal jelly, has shown promising anti-neuroinflammatory, blood–brain barrier (BBB)-preserving, and neurogenesis-promoting properties. In this paper, we provide a summary of the relationship between MetS and AD, together with an introduction to 10-HDA as a potential intervention nutrient. In addition, molecular docking is performed to explore the metabolic tuning properties of 10-HDA with associated macromolecules such as GLP-1R, PPARs, GSK-3, and TREM2. In conclusion, there is a close relationship between AD and MetS, and 10-HDA shows potential as a beneficial nutritional intervention for both AD and MetS.

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Section: Metabolic Syndrome and Alzheimer’s Diseasementioning

confidence: 99%

Metabolic Profile of Alzheimer’s Disease: Is 10-Hydroxy-2-decenoic Acid a Pertinent Metabolic Adjuster?

Gong,

Luo,

et al. 2023

Metabolites

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show abstract

“…As a metabolic disorder, diabetes affects more than 400 million patients and an estimated 193 million undiagnosed people worldwide, of which more than 90% are type 2 diabetes (T2D) 6 . Studies have shown that AD and diabetes are not independent diseases; instead, they are often closely linked at clinical and pathophysiological levels 7–10 . For example, diabetes is among the most common comorbidities of AD, with 25%–35% of AD patients suffering from T2D 11,12 .…”

Section: Introductionmentioning

confidence: 99%

“… 6 Studies have shown that AD and diabetes are not independent diseases; instead, they are often closely linked at clinical and pathophysiological levels. 7 , 8 , 9 , 10 For example, diabetes is among the most common comorbidities of AD, with 25%–35% of AD patients suffering from T2D. 11 , 12 While in patients with diabetes, significant cognitive impairments are often observed.…”

Section: Introductionmentioning

confidence: 99%

Hypericin as a potential drug for treating Alzheimer's disease and type 2 diabetes with a view to drug repositioning

et al. 2023

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AimsAlzheimer's disease (AD) and type 2 diabetes (T2D) are two of the most common diseases in elderly population and they have a high rate of comorbidity. Study has revealed that T2D is a major risk factor of AD, and thus exploring therapeutic approaches that can target both diseases has drawn much interest in recent years. In this study, we tried to explore drugs that could be potentially used to prevent or treat both AD and T2D via a drug repositioning approach.MethodsWe first searched the known drugs that may be effective to T2D treatment based on the network distance between the T2D‐associated genes and drugs deposited in the DrugBank database. Then, via molecular docking, we further screened these drugs by examining their interaction with islet amyloid polypeptide (IAPP) and Aβ42 peptide, the key components involved in the pathogenesis of T2D or AD. Finally, the binding between the selected drug candidates and the target proteins was verified by molecular dynamics (MD) simulation; and the potential function of the drug candidates and the corresponding targets were analyzed.ResultsFrom multiple resources, 734 T2D‐associated genes were collected, and a list of 1109 drug candidates for T2D was obtained. We found that hypericin had the lowest binding energy and the most stable interaction with either IAPP or Aβ42 peptide. In addition, we also found that the target genes regulated by hypericin were differentially expressed in the tissues related to the two diseases.ConclusionOur results show that hypericin may be able to bind with IAPP and Aβ42 stably and prevent their accumulation, and thus could be a promising drug candidate for treating the comorbidity of AD and T2D.

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Huperzine A ameliorates obesity-related cognitive performance impairments involving neuronal insulin signaling pathway in mice

Wang

Diao

et al. 2019

Acta Pharmacol Sin

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Type 2 diabetes (T2D) and Alzheimer’s disease (AD) share several common pathophysiological features. Huperzine A (Hup A), a Lycopodium alkaloid extracted from the Chinese herb moss Huperzia serrata , is a specific and reversible inhibitor of acetylcholinesterase, which is clinically used for the treatment of AD. In this study, we investigated whether Hup A improved the metabolic and cognitive functions in the high fat-induced (HFD) obese mice and genetic ob/ob mice. HFD and ob/ob mice were treated with Hup A (0.1, 0.3 mg · kg −1 · d −1 , ig) for 3 months. Body weight was monitored and glucose tolerance tests were performed. Novel object recognition test and Morris water maze assay were conducted to evaluate the cognitive functions. We found that the Hup A treatment had no significant effect on peripheral metabolism of obese mice, whereas Hup A (0.1, mg · kg −1 · d −1 ) improved both the abilities of object recognition and spatial memory in HFD-fed mice, but not in ob/ob mice. Furthermore, Hup A treatment significantly upregulated the insulin and phosphorylated Akt levels in the cortex of HFD-fed mice, but not ob/ob mice. In addition, Hup A (0.3, mg · kg −1 · d −1 ) significantly decreased cortical β-secretase (BACE1) expression. In conclusion, these results demonstrate that treatment with Hup A (0.1, mg · kg −1 · d −1 ) can effectively improve the cognitive functions, at least in diet-induced obese mice.

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A Potential New Mechanism Linking Type II Diabetes Mellitus and Alzheimer's Disease

Cited by 4 publications

References 7 publications

Metabolic Profile of Alzheimer’s Disease: Is 10-Hydroxy-2-decenoic Acid a Pertinent Metabolic Adjuster?

Metabolic Profile of Alzheimer’s Disease: Is 10-Hydroxy-2-decenoic Acid a Pertinent Metabolic Adjuster?

Hypericin as a potential drug for treating Alzheimer's disease and type 2 diabetes with a view to drug repositioning

Huperzine A ameliorates obesity-related cognitive performance impairments involving neuronal insulin signaling pathway in mice

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