A novel approach to type 3 diabetes mechanism: The interplay between noncoding RNAs and insulin signaling pathway in Alzheimer's disease

Moayedi, Kiana; Orandi, Shirin; Ebrahimi, Reyhane; Tanhapour, Maryam; Moradi, Mona; Abbastabar, Maryam; Golestani, Abolfazl

doi:10.1002/jcp.30779

Cited by 8 publications

(6 citation statements)

References 218 publications

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“…DM is the most common metabolic disorder and the direct cause of its occurrence is usually due to defective insulin action or insufficient insulin secretion ( 20 , 21 ). Several real-world clinical cases suggest that brain-related mild cognitive impairment complications in diabetes may lead to cognitive deficits, which gradually develops into AD ( 22 , 23 ).…”

Section: Metabolic Diseases and Admentioning

confidence: 99%

Alzheimer's disease, a metabolic disorder: Clinical advances and basic model studies (Review)

Zhou,

Tu,

Chen

et al. 2023

Exp Ther Med

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Alzheimer's disease (AD) is a type of neurodegenerative disease characterized by cognitive impairment that is aggravated with age. The pathological manifestations include extracellular amyloid deposition, intracellular neurofibrillary tangles and loss of neurons. As the world population ages, the incidence of AD continues to increase, not only posing a significant threat to the well-being and health of individuals but also bringing a heavy burden to the social economy. There is epidemiological evidence suggesting a link between AD and metabolic diseases, which share pathological similarities. This potential link would deserve further consideration; however, the pathogenesis and therapeutic efficacy of AD remain to be further explored. The complex pathogenesis and pathological changes of AD pose a great challenge to the choice of experimental animal models. To understand the role of metabolic diseases in the development of AD and the potential use of drugs for metabolic diseases, the present article reviews the research progress of the comorbidity of AD with diabetes, obesity and hypercholesterolemia, and summarizes the different roles of animal models in the study of AD to provide references for researchers.

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Section: Metabolic Diseases and Admentioning

confidence: 99%

Alzheimer's disease, a metabolic disorder: Clinical advances and basic model studies (Review)

Zhou,

Tu,

Chen

et al. 2023

Exp Ther Med

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“…In addition, it is reported that the dysregulation of β‐site amyloid precursor protein cleaving enzyme 1 (BACE1), a key gene involved in the production of Aβ in the brain, can lead to both AD‐like symptoms and the development of diabetic complications 25 . Thus, AD is sometimes referred to as diabetes type 3 26,27 …”

Section: Introductionmentioning

confidence: 99%

“…25 Thus, AD is sometimes referred to as diabetes type 3. 26,27 In recent years, there is a growing interest in repositioning existing antidiabetic drugs for other diseases, and a few of them have shown great potential for treating cancer, neurodegenerative diseases, or cardiovascular diseases. 28 Considering the close connection between AD and T2D, using medications that are already used to for diabetes to treat AD has drawn much attention.…”

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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“…Diabetes and dementia are often comorbid in ageing individuals, 10 thus a link between the two conditions is implied. Of note, insulin resistance in the brain has been referred to as ‘type 3 diabetes’, and is considered a major driving force in the pathophysiology of AD 11,12 …”

Section: Introductionmentioning

confidence: 99%

“…Of note, insulin resistance in the brain has been referred to as 'type 3 diabetes', and is considered a major driving force in the pathophysiology of AD. 11,12 Over the last several decades, diabetes has become an established risk factor for cognitive decline and dementia, yet the extent to which each subtype of dementia (notably AD and VaD) is implicated remains controversial, and the impact of treatment remains uncertain. 5,13,14 We therefore aimed to conduct a systematic umbrella review of the evidence linking diabetes and its treatment to risk of dementia, as well as an updated meta-analysis on the association between antidiabetic treatment and incident dementia.…”

Section: Introductionmentioning

confidence: 99%

Diabetes, antidiabetic medications and risk of dementia: A systematic umbrella review and meta‐analysis

Kuate Defo,

Bakula,

Pisaturo

et al. 2023

Diabetes Obesity Metabolism

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AimsThe objective of this umbrella review and meta‐analysis was to evaluate the effect of diabetes on risk of dementia, as well as the mitigating effect of antidiabetic treatments.Materials and MethodsWe conducted a systematic umbrella review on diabetes and its treatment, and a meta‐analysis focusing on treatment. We searched MEDLINE/PubMed, Embase, PsycINFO, CINAHL and the Cochrane Library for systematic reviews and meta‐analyses assessing the risk of cognitive decline/dementia in individuals with diabetes until 2 July 2023. We conducted random‐effects meta‐analyses to obtain risk ratios and 95% confidence intervals estimating the association of metformin, thiazolidinediones, pioglitazone, dipeptidyl peptidase‐4 inhibitors, α‐glucosidase inhibitors, meglitinides, insulin, sulphonylureas, glucagon‐like peptide‐1 receptor agonists (GLP1RAs) and sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) with risk of dementia from cohort/case‐control studies. The subgroups analysed included country and world region. Risk of bias was assessed with the AMSTAR tool and Newcastle‐Ottawa Scale.ResultsWe included 100 reviews and 27 cohort/case‐control studies (N = 3 046 661). Metformin, thiazolidinediones, pioglitazone, GLP1RAs and SGLT2is were associated with significant reduction in risk of dementia. When studies examining metformin were divided by country, the only significant effect was for the United States. Moreover, the effect of metformin was significant in Western but not Eastern populations. No significant effect was observed for dipeptidyl peptidase‐4 inhibitors, α‐glucosidase inhibitors, or insulin, while meglitinides and sulphonylureas were associated with increased risk.ConclusionsMetformin, thiazolidinediones, pioglitazone, GLP1RAs and SGLT2is were associated with reduced risk of dementia. More longitudinal studies aimed at determining their relative benefit in different populations should be conducted.

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A novel approach to type 3 diabetes mechanism: The interplay between noncoding RNAs and insulin signaling pathway in Alzheimer's disease

Cited by 8 publications

References 218 publications

Alzheimer's disease, a metabolic disorder: Clinical advances and basic model studies (Review)

Alzheimer's disease, a metabolic disorder: Clinical advances and basic model studies (Review)

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

Diabetes, antidiabetic medications and risk of dementia: A systematic umbrella review and meta‐analysis

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