A Pathophysiological Intersection of Diabetes and Alzheimer’s Disease

Čater, Maša; Hölter, Sabine M.

doi:10.3390/ijms231911562

Cited by 7 publications

(3 citation statements)

References 183 publications

(226 reference statements)

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“…Compelling recent literature has shown numerous associations between AD and metabolic disease. For example, insulin resistance and impaired glucose metabolism have important roles in the pathophysiology of dementia, cognitive decline, and AD [ 6 ]. Mitochondrial dysfunction, a common factor seen in both AD and T2DM, could lead to energy shortages in the hippocampus, potentially explaining the memory impairment commonly found in AD [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

The Geroprotective Drug Candidate CMS121 Alleviates Diabetes, Liver Inflammation, and Renal Damage in db/db Leptin Receptor Deficient Mice

Zahid

Dafre

Currais

et al. 2023

IJMS

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db/db mice, which lack leptin receptors and exhibit hyperphagia, show disturbances in energy metabolism and are a model of obesity and type 2 diabetes. The geroneuroprotector drug candidate CMS121 has been shown to be effective in animal models of Alzheimer’s disease and aging through the modulation of metabolism. Thus, the hypothesis was that CMS121 could protect db/db mice from metabolic defects and thereby reduce liver inflammation and kidney damage. The mice were treated with CMS121 in their diet for 6 months. No changes were observed in food and oxygen consumption, body mass, or locomotor activity compared to control db/db mice, but a 5% reduction in body weight was noted. Improved glucose tolerance and reduced HbA1c and insulin levels were also seen. Blood and liver triglycerides and free fatty acids decreased. Improved metabolism was supported by lower levels of fatty acid metabolites in the urine. Markers of liver inflammation, including NF-κB, IL-18, caspase 3, and C reactive protein, were lowered by the CMS121 treatment. Urine markers of kidney damage were improved, as evidenced by lower urinary levels of NGAL, clusterin, and albumin. Urine metabolomics studies provided further evidence for kidney protection. Mitochondrial protein markers were elevated in db/db mice, but CMS121 restored the renal levels of NDUFB8, UQCRC2, and VDAC. Overall, long-term CMS121 treatment alleviated metabolic imbalances, liver inflammation, and reduced markers of kidney damage. Thus, this study provides promising evidence for the potential therapeutic use of CMS121 in treating metabolic disorders.

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Section: Introductionmentioning

confidence: 99%

The Geroprotective Drug Candidate CMS121 Alleviates Diabetes, Liver Inflammation, and Renal Damage in db/db Leptin Receptor Deficient Mice

Zahid

Dafre

Currais

et al. 2023

IJMS

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“…Several epidemiological and clinical studies have suggested a possible shared pathophysiology between diabetes and AD, and the administration of certain antidiabetic medications, such as intranasal insulin, metformin, incretins, and thiazolidinediones, has been shown to improve cognition and memory in patients with mild cognitive impairment and AD. As a result, the term “type 3 diabetes” has been proposed for AD, considering it a metabolic disease caused by insulin resistance and insulin-like growth factor in the brain ( Čater and Hölter, 2022 ). Additionally, antidiabetic drugs such as metformin have been observed to improve insulin sensitivity and reduce inflammation in the brain, suggesting that they could slow or reverse the process of cognitive decline in patients with AD.…”

Section: Resultsmentioning

confidence: 99%

Mapping new pharmacological interventions for cognitive function in Alzheimer’s disease: a systematic review of randomized clinical trials

et al. 2023

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Background and Objective: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, that is, characterized by cognitive decline. To date, there are no effective treatments for AD. Therefore, the objective of this study was to map new perspectives on the effects of pharmacological treatment on cognitive function and the overall psychological state in patients with AD.Methods: Two independent researchers searched for randomized clinical trials (RCTs) exploring new pharmacological approaches related to cognition in Alzheimer’s disease in adults from 2018 to 2023 in PubMed, Web of Science, Scopus, and Cochrane Library databases. A total of 17 RCTs were included in this review.Results: The results show that in recent years, new drugs have been tested in patients with Alzheimer’s disease, including masitinib, methylphenidate, levetiracetam, Jiannao Yizhi, and Huannao Yicong formulas. Most studies have been conducted in populations with mild to moderate Alzheimer’s disease.Conclusion: Although some of the drugs found suggested improvement in cognitive function, the scarcity of available studies highlights the need for further research in this area.Systematic review registration: [www.crd.york.ac.uk/prospero], identifier [CRD42023409986].

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“…Currently, there is a growing body of evidence indicating a strong link between metabolic disorders and Alzheimer’s disease ( St. John-Williams et al, 2019 ; Mejido et al, 2020 ; Sultana et al, 2023 ), metabolic disorders are considered a significant cause of AD ( Poddar et al, 2021 ). In particular, the imbalances in lipid metabolism, insulin resistance, and the resultant conditions of obesity and diabetes are viewed as potential risk factors for AD ( Robinson et al, 2017 ; Čater and Hölter, 2022 ). Hence, metabolic pathways may themselves contain promising therapeutic targets for AD ( Cai et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Tauroursodeoxycholic acid: a bile acid that may be used for the prevention and treatment of Alzheimer’s disease

Song,

Liu,

Wang

et al. 2024

Front. Neurosci.

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Alzheimer’s disease (AD) is a prevalent neurodegenerative disease that has become one of the main factors affecting human health. It has serious impacts on individuals, families, and society. With the development of population aging, the incidence of AD will further increase worldwide. Emerging evidence suggests that many physiological metabolic processes, such as lipid metabolism, are implicated in the pathogenesis of AD. Bile acids, as the main undertakers of lipid metabolism, play an important role in the occurrence and development of Alzheimer’s disease. Tauroursodeoxycholic acid, an endogenous bile acid, has been proven to possess therapeutic effects in different neurodegenerative diseases, including Alzheimer’s disease. This review tries to find the relationship between bile acid metabolism and AD, as well as explore the therapeutic potential of bile acid taurocursodeoxycholic acid for this disease. The potential mechanisms of taurocursodeoxycholic acid may include reducing the deposition of Amyloid-β protein, regulating apoptotic pathways, preventing tau hyperphosphorylation and aggregation, protecting neuronal synapses, exhibiting anti-inflammatory properties, and improving metabolic disorders. The objective of this study is to shed light on the use of tauroursodeoxycholic acid preparations in the prevention and treatment of AD, with the aim of identifying effective treatment targets and clarifying various treatment mechanisms involved in this disease.

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A Pathophysiological Intersection of Diabetes and Alzheimer’s Disease

Cited by 7 publications

References 183 publications

The Geroprotective Drug Candidate CMS121 Alleviates Diabetes, Liver Inflammation, and Renal Damage in db/db Leptin Receptor Deficient Mice

The Geroprotective Drug Candidate CMS121 Alleviates Diabetes, Liver Inflammation, and Renal Damage in db/db Leptin Receptor Deficient Mice

Mapping new pharmacological interventions for cognitive function in Alzheimer’s disease: a systematic review of randomized clinical trials

Tauroursodeoxycholic acid: a bile acid that may be used for the prevention and treatment of Alzheimer’s disease

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