scholarly journals Metformin a Potential Pharmacological Strategy in Late Onset Alzheimer’s Disease Treatment

2021 ◽  
Vol 14 (9) ◽  
pp. 890
Author(s):  
Saghar Rabiei Poor ◽  
Miren Ettcheto ◽  
Amanda Cano ◽  
Elena Sanchez-Lopez ◽  
Patricia Regina Manzine ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Adenosine Monophosphate ◽  
Sirtuin 1 ◽  
Health Concern ◽  
Therapeutic Effects ◽  
Age Related

Alzheimer’s disease (AD) is one of the most devastating brain disorders. Currently, there are no effective treatments to stop the disease progression and it is becoming a major public health concern. Several risk factors are involved in the progression of AD, modifying neuronal circuits and brain cognition, and eventually leading to neuronal death. Among them, obesity and type 2 diabetes mellitus (T2DM) have attracted increasing attention, since brain insulin resistance can contribute to neurodegeneration. Consequently, AD has been referred to “type 3 diabetes” and antidiabetic medications such as intranasal insulin, glitazones, metformin or liraglutide are being tested as possible alternatives. Metformin, a first line antihyperglycemic medication, is a 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activator hypothesized to act as a geroprotective agent. However, studies on its association with age-related cognitive decline have shown controversial results with positive and negative findings. In spite of this, metformin shows positive benefits such as anti-inflammatory effects, accelerated neurogenesis, strengthened memory, and prolonged life expectancy. Moreover, it has been recently demonstrated that metformin enhances synaptophysin, sirtuin-1, AMPK, and brain-derived neuronal factor (BDNF) immunoreactivity, which are essential markers of plasticity. The present review discusses the numerous studies which have explored (1) the neuropathological hallmarks of AD, (2) association of type 2 diabetes with AD, and (3) the potential therapeutic effects of metformin on AD and preclinical models.

scholarly journals Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy

2019 ◽  
Vol 9 (10) ◽  
pp. 262 ◽  
Author(s):  
Hayden
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Late Onset ◽  
Neurovascular Unit ◽  
Age Related ◽  
Increased Risk

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease–dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments and metabolic factors, which increase the cellular vulnerability to develop an increased risk of age-related LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. Aging (chronic age-related diseases); ii. metabolic (hyperglycemia advanced glycation end products and its receptor (AGE/RAGE) interactions and hyperinsulinemia-insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen–nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis—vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.

scholarly journals Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy

2019 ◽  
Author(s):  
Melvin Hayden
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Late Onset ◽  
Neurovascular Unit ◽  
Age Related ◽  
Increased Risk

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease-dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments associated with metabolic factors and increases the cellular vulnerability to develop the age-related increased risk of LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. aging (chronic age-related diseases); ii. metabolic (hyperglycemia - advanced glycation end-products and its receptor (AGE/RAGE) interactions and hyperinsulinemia – insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen-nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis - vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.

scholarly journals Type 2 Diabetes and Late-Onset Alzheimer’s Disease

2011 ◽  
Vol 31 (6) ◽  
pp. 424-430 ◽  
Author(s):  
D. Cheng ◽  
J. Noble ◽  
M.X. Tang ◽  
N. Schupf ◽  
R. Mayeux ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Late Onset

Green coffee as a novel agent for Alzheimer’s disease prevention by attenuating diabetes

2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Merina Varghese ◽  
Lap Ho ◽  
Jun Wang ◽  
Wei Zhao ◽  
Samara Levine ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Coffee Consumption ◽  
Diabetes Type 2 ◽  
Health Concern ◽  
Protective Effects ◽  
Green Coffee ◽  
Active Components

AbstractDiabetes type 2, caused mainly by insulin resistance, is growing in incidence worldwide. In addition to being a major public health concern, type 2 diabetes is also a risk factor for dementia, including Alzheimer’s disease type dementia. Coffee consumption is reported to have protective effects in both diabetes and Alzheimer’s disease. We review here the reported beneficial effects of coffee in both disease conditions and the previously identified active ingredients of coffee. Furthermore, we revisit our recent findings of improved glucose utilization in the periphery and in the brain in a mouse model of high-fat diet induced type 2 diabetes after treatment with a decaffeinated green coffee preparation. Overall, consumption of coffee appears to improve diabetes and reduce the risk of dementia, although future studies are required to further identify the active components and the type of coffee that is most effective in addressing these conditions.

Screening Traditional Chinese Medicine Combination for Cotreatment of Alzheimer’s Disease and Type 2 Diabetes Mellitus by Network Pharmacology

2021 ◽  
pp. 1-11
Author(s):  
Yi-Zhen Wang ◽  
Lei Meng ◽  
Qi-Shuai Zhuang ◽  
Liang Shen
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Network Pharmacology ◽  
Therapeutic Effects

Background: In recent years, the efficacy of type 2 diabetes mellitus (T2DM) drugs in the treatment of Alzheimer’s disease (AD) has attracted extensive interest owing to the close associations between the two diseases. Objective: Here, we screened traditional Chinese medicine (TCM) and multi-target ingredients that may have potential therapeutic effects on both T2DM and AD from T2DM prescriptions. Methods: Network pharmacology and molecular docking were used. Results: Firstly, the top 10 frequently used herbs and corresponding 275 active ingredients were identified from 263 T2DM-related TCM prescriptions. Secondly, through the comparative analysis of 208 potential targets of ingredients, 1,740 T2DM-related targets, and 2,060 AD-related targets, 61 common targets were identified to be shared. Thirdly, by constructing pharmacological network, 26 key targets and 154 representative ingredients were identified. Further enrichment analysis showed that common targets were involved in regulating multiple pathways related to T2DM and AD, while network analysis also found that the combination of Danshen (Radix Salviae)-Gancao (Licorice)-Shanyao (Rhizoma Dioscoreae) contained the vast majority of the representative ingredients and might be potential for the cotreatment of the two diseases. Fourthly, MAPK1, PPARG, GSK3B, BACE1, and NR3C1 were selected as potential targets for virtual screening of multi-target ingredients. Further docking studies showed that multiple natural compounds, including salvianolic acid J, gancaonin H, gadelaidic acid, icos-5-enoic acid, and sigmoidin-B, exhibited high binding affinities with the five targets. Conclusion: To summarize, the present study provides a potential TCM combination that might possess the potential advantage of cotreatment of AD and T2DM.

scholarly journals Role of FoxO transcription factors in aging and age-related metabolic and neurodegenerative diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuqi Du ◽  
Hui Zheng
Keyword(s):  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Transcription Factors ◽  
Living Standard ◽  
Past Century ◽  
Age Related ◽  
Foxo Transcription Factors

AbstractAging happens to all of us as we live. Thanks to the improved living standard and discovery of life-saving medicines, our life expectancy has increased substantially across the world in the past century. However, the rise in lifespan leads to unprecedented increases in both the number and the percentage of individuals 65 years and older, accompanied by the increased incidences of age-related diseases such as type 2 diabetes mellitus and Alzheimer’s disease. FoxO transcription factors are evolutionarily conserved molecules that play critical roles in diverse biological processes, in particular aging and metabolism. Their dysfunction is often found in the pathogenesis of many age-related diseases. Here, we summarize the signaling pathways and cellular functions of FoxO proteins. We also review the complex role of FoxO in aging and age-related diseases, with focus on type 2 diabetes and Alzheimer’s disease and discuss the possibility of FoxO as a molecular link between aging and disease risks.

scholarly journals Sirtuin-1 mediates the obesity induced risk of common degenerative diseases: Alzheimer’s disease, coronary artery disease and type 2 diabetes

Health ◽  
2012 ◽  
Vol 04 (12) ◽  
pp. 1448-1456 ◽  
Author(s):  
Ian James Martins ◽  
Andrea. C. Wilson ◽  
Wei Ling Florence Lim ◽  
Simon. M. Laws ◽  
Stephanie. J. Fuller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Alzheimer's Disease ◽  
Coronary Artery ◽  
Sirtuin 1 ◽  
Degenerative Diseases ◽  
Artery Disease
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