Cellular and molecular mechanisms of Dementia: Decoding the causal link of Diabetes Mellitus in Alzheimer’s disease

2021 ◽  
Vol 20 ◽  
Author(s):  
Mahmood Rasool ◽  
Arif Malik ◽  
Sulayman Waquar ◽  
Ahmad Zaheer ◽  
Muhammad Asif ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pancreatic Beta Cells ◽  
Molecular Mechanisms ◽  
Neuronal Degeneration ◽  
Insulin Receptors ◽  
Causal Link ◽  
Patients With Diabetes ◽  
Amyloid Beta Proteins

: Dementia and diabetes are the two major disorders that are linked at both biochemical and molecular levels which is due to the existing similarities between pancreatic beta-cells and neuronal cells at the transcription and translational levels. Both diseases have similar causative genes or factors and dementia is one of the advanced complications in about 50-52% of patients with type 2 diabetes mellitus (T2DM). Further, patients with T2DM are at a higher risk of neuronal degeneration and Alzheimer’s disease (AD). Dementia, which is most common in AD, is associated with diminished insulin receptors by nearly 80%. The impairment in insulin signaling thus leads to the development of dementia and AD. Biochemical changes in ‘tau’ protein and amyloid-beta proteins, make them critical players in the formation of plaques in patients with dementia and AD. Here, we decode various cellular and molecular mechanisms associated with the development of dementia in patients with diabetes and AD.

scholarly journals Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1236
Author(s):  
Jesús Burillo ◽  
Patricia Marqués ◽  
Beatriz Jiménez ◽  
Carlos González-Blanco ◽  
Manuel Benito ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Progressive Disease

Type 2 diabetes mellitus is a progressive disease that is characterized by the appearance of insulin resistance. The term insulin resistance is very wide and could affect different proteins involved in insulin signaling, as well as other mechanisms. In this review, we have analyzed the main molecular mechanisms that could be involved in the connection between type 2 diabetes and neurodegeneration, in general, and more specifically with the appearance of Alzheimer’s disease. We have studied, in more detail, the different processes involved, such as inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.

A Tale of Two Diseases: Exploring Mechanisms Linking Diabetes Mellitus with Alzheimer’s Disease

2021 ◽  
pp. 1-17
Author(s):  
Jessica Lynn ◽  
Mingi Park ◽  
Christiana Ogunwale ◽  
George K. Acquaah-Mensah
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Mammalian Target Of Rapamycin ◽  
Insulin Receptors ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Main Component ◽  
The Impact

Dementias, including the type associated with Alzheimer’s disease (AD), are on the rise worldwide. Similarly, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases globally. Although mechanisms and treatments are well-established for T2DM, there remains much to be discovered. Recent research efforts have further investigated factors involved in the etiology of AD. Previously perceived to be unrelated diseases, commonalities between T2DM and AD have more recently been observed. As a result, AD has been labeled as “type 3 diabetes”. In this review, we detail the shared processes that contribute to these two diseases. Insulin resistance, the main component of the pathogenesis of T2DM, is also present in AD, causing impaired brain glucose metabolism, neurodegeneration, and cognitive impairment. Dysregulation of insulin receptors and components of the insulin signaling pathway, including protein kinase B, glycogen synthase kinase 3β, and mammalian target of rapamycin are reported in both diseases. T2DM and AD also show evidence of inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, and amyloid deposition. The impact that changes in neurovascular structure and genetics have on the development of these conditions is also being examined. With the discovery of factors contributing to AD, innovative treatment approaches are being explored. Investigators are evaluating the efficacy of various T2DM medications for possible use in AD, including but not limited to glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor-gamma agonists. Furthermore, there are 136 active trials involving 121 therapeutic agents targeting novel AD biomarkers. With these efforts, we are one step closer to alleviating the ravaging impact of AD on our communities.

scholarly journals Alzheimer’s Disease and Type 2 Diabetes Mellitus: Molecular Mechanisms and Similarities

2020 ◽  
Author(s):  
Karla Isabel Lira-De León ◽  
Alma Delia Bertadillo-Jilote ◽  
David Gustavo García-Gutiérrez ◽  
Marco Antonio Meraz-Ríos
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Molecular Mechanisms

Global View on Alzheimer’s Disease and Diabetes Mellitus: Threats, Risks and Treatment Alzheimer’s Disease and Diabetes Mellitus

2018 ◽  
Vol 15 (14) ◽  
pp. 1277-1282 ◽  
Author(s):  
Blanka Klimova ◽  
Kamil Kuca ◽  
Petra Maresova
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Economic Threat ◽  
Patients With Diabetes ◽  
Randomized Control ◽  
The Relationship ◽  
Positive Effect

The incidence of both diabetes and Alzheimer’s disease (AD) is increasing and is becoming a social and economic threat worldwide. Recent research studies indicate that both diseases share some pathophysiological features and that specifically, Type 2 Diabetes Mellitus (T2DM) is a risk factor of Alzheimer’s disease. The aim of this study is to explore the relationship between diabetes mellitus and AD, explore the efficacy of selected drugs on patients with diabetes and AD, and compare the relative risk of diabetes for Alzheimer’s disease within different clinical studies. The method of literature search in several acknowledged databases such as Web of Science, Elsevier Science Direct, PubMed and Scopus in the period from 2000 to 2015 for the following keywords: “Alzheimer’s AND disease AND diabetes AND mellitus” was used. The identified studies were divided into two basic groups, based on their focus: efficacy of the selected drugs on patients suffering from AD and diabetes, and a link between diabetes and AD; as diabetes is seen as a risk factor of AD. The findings of this study confirm that there is a close and direct link between diabetes and AD, which indicates that there is a need for early diagnosis of metabolic syndrome, insulin resistance, and T2DM. In fact, the reviewed clinical trials have proved an increase in the risk of AD. However, the values of this risk are relatively low. The results also illustrate that both pharmacological (e.g., the antidiabetic drugs together with insulin dosing) and nonpharmacological (e.g., being intensively engaged in physical activities) treatments can have a positive effect. The results of this study confirm that diabetes and AD are not independent disorders since they share some common pathophysiological mechanisms. In addition, more clinical randomized control trials are needed to explore the efficacy of both pharmacological and non-pharmacological approaches to the treatment of T2DM and AD.

scholarly journals Data-Driven Modeling of Knowledge Assemblies in Understanding Comorbidity Between Type 2 Diabetes Mellitus and Alzheimer’s Disease

2020 ◽  
Vol 78 (1) ◽  
pp. 87-95
Author(s):  
Reagon Karki ◽  
Sumit Madan ◽  
Yojana Gadiya ◽  
Daniel Domingo-Fernández ◽  
Alpha Tom Kodamullil ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Genetic Variants ◽  
Molecular Mechanisms ◽  
Meta Analysis ◽  
Relevant Literature

Background: Recent studies have suggested comorbid association between Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) through identification of shared molecular mechanisms. However, the inference is pre-dominantly literature-based and lacks interpretation of pre-disposed genomic variants and transcriptomic measurables. Objective: In this study, we aim to identify shared genetic variants and dysregulated genes in AD and T2DM and explore their functional roles in the comorbidity between the diseases. Methods: The genetic variants for AD and T2DM were retrieved from GWAS catalog, GWAS central, dbSNP, and DisGeNet and subjected to linkage disequilibrium analysis. Next, shared variants were prioritized using RegulomeDB and Polyphen-2. Afterwards, a knowledge assembly embedding prioritized variants and their corresponding genes was created by mining relevant literature using Biological Expression Language. Finally, coherently perturbed genes from gene expression meta-analysis were mapped to the knowledge assembly to pinpoint biological entities and processes and depict a mechanistic link between AD and T2DM. Results: Our analysis identified four genes (i.e., ABCG1, COMT, MMP9, and SOD2) that could have dual roles in both AD and T2DM. Using cartoon representation, we have illustrated a set of causal events surrounding these genes which are associated to biological processes such as oxidative stress, insulin resistance, apoptosis and cognition. Conclusion: Our approach of using data as the driving force for unraveling disease etiologies eliminates literature bias and enables identification of novel entities that serve as the bridge between comorbid conditions.

Molecular and Biochemical Pathways Encompassing Diabetes Mellitus and Dementia

2021 ◽  
Vol 20 ◽  
Author(s):  
Tapan Behl ◽  
Arpita Arora ◽  
Aayush Sehgal ◽  
Sukhbir Singh ◽  
Neelam Sharma ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Vicious Cycle ◽  
Early Therapy ◽  
Impaired Insulin ◽  
The Brain

: Diabetes mellitus is a major metabolic disorder that has now emerged as an epidemic, and it affects the brain through an array of pathways. Diabetes mellitus patients can develop pathological changes in the brain, which eventually take the shape of mild cognitive impairment progressing to Alzheimer’s Disease. A number of preclinical and clinical studies demonstrate this fact, and it comes out to be those molecular pathways such as amyloidogenesis, oxidative stress, inflammation, and impaired insulin signaling are identical in diabetes mellitus and dementia. However, the critical player involved in the vicious cycle of diabetes mellitus and dementia is insulin, whose signaling, when impaired in diabetes mellitus (both type 1 and 2), leads to a decline in cognition, although other pathways are also essential contributors. Moreover, it is not only that diabetes mellitus patients indicate cognitive decline at a later stage; many Alzheimer’s Disease patients also reflect symptoms of diabetes mellitus, thus creating a vicious cycle inculcating a web of complex molecular mechanisms and hence categorizing Alzheimer’s Disease as ‘brain diabetes’. Thus, it is practical to suggest that anti-diabetic drugs are beneficial in Alzheimer’s Disease; but only smaller trials, not the larger ones, have showcased positive outcomes mainly because of the late onset of therapy. Therefore, it is extremely important to develop more of such molecules that target insulin in dementia patients along with such methods that diagnose impaired insulin signaling and the associated cognitive decline so that early therapy may be initiated and the progression of the disease be prevented.

scholarly journals The Action of Polyphenols in Diabetes Mellitus and Alzheimer's Disease: A Common Agent for Overlapping Pathologies

2019 ◽  
Vol 17 (7) ◽  
pp. 590-613 ◽  
Author(s):  
Ana C. Silveira ◽  
Jane Pires Dias ◽  
Vanessa M. Santos ◽  
Pedro Fontes Oliveira ◽  
Marco G. Alves ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fruits And Vegetables ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Genetic Alterations ◽  
Therapeutic Alternatives ◽  
The Relationship

:Diabetes Mellitus (DM) and Alzheimer's disease (AD) are two prevalent diseases in modern societies, which are caused mainly by current lifestyle, aging and genetic alterations. It has already been demonstrated that these two diseases are associated, since individuals suffering from DM are prone to develop AD. Conversely, it is also known that individuals with AD are more susceptible to DM, namely type 2 diabetes (T2DM). Therefore, these two pathologies, although completely different in terms of symptomatology, end up sharing several mechanisms at the molecular level, with the most obvious being the increase of oxidative stress and inflammation.:Polyphenols are natural compounds widely spread in fruits and vegetables whose dietary intake has been considered inversely proportional to the incidence of DM and AD. So, it is believed that this group of phytochemicals may have preventive and therapeutic potential, not only by reducing the risk and delaying the development of these pathologies, but also by improving brain’s metabolic profile and cognitive function.:The aim of this review is to understand the extent to which DM and AD are related pathologies, the degree of similarity and the relationship between them, to detail the molecular mechanisms by which polyphenols may exert a protective effect, such as antioxidant and anti-inflammatory effects, and highlight possible advantages of their use as common preventive and therapeutic alternatives.

scholarly journals Effects and Underlying Mechanisms of Bioactive Compounds on Type 2 Diabetes Mellitus and Alzheimer’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-25 ◽  
Author(s):  
Rongzi Li ◽  
Yuxian Zhang ◽  
Suhail Rasool ◽  
Thangiah Geetha ◽  
Jeganathan Ramesh Babu
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Bioactive Compounds ◽  
Molecular Mechanisms ◽  
Clinical Effects ◽  
Brain Disorder

Type 2 diabetes mellitus is a complicated metabolic disorder characterized by hyperglycemia and glucose intolerance. Alzheimer’s disease is a progressive brain disorder characterized by a chronic loss of cognitive and behavioral function. Considering the shared characteristics of both diseases, common therapeutic and preventive agents may be effective. Bioactive compounds such as polyphenols, vitamins, and carotenoids found in vegetables and fruits can have antioxidant and anti-inflammatory effects. These effects make them suitable candidates for the prevention or treatment of diabetes and Alzheimer’s disease. Increasing evidence from cell or animal models suggest that bioactive compounds may have direct effects on decreasing hyperglycemia, enhancing insulin secretion, and preventing formation of amyloid plaques. The possible underlying molecular mechanisms are described in this review. More studies are needed to establish the clinical effects of bioactive compounds.

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