Interlink Between Insulin Resistance and Neurodegeneration with an Update on Current Therapeutic Approaches

2020 ◽  
Vol 19 (3) ◽  
pp. 174-183
Author(s):  
Subrat Kumar Bhattamisra ◽  
Lee Yuen Shin ◽  
Hanis Izzati Binti Mohd Saad ◽  
Vikram Rao ◽  
Mayuren Candasamy ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Insulin Signaling ◽  
Therapeutic Approaches ◽  
The Brain

The interlink between diabetes mellitus and neurodegenerative diseases such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) has been identified by several researchers. Patients with Type-2 Diabetes Mellitus (T2DM) are found to be affected with cognitive impairments leading to learning and memory deficit, while patients with Type-1 Diabetes Mellitus (T1DM) showed less severe levels of these impairments in the brain. This review aimed to discuss the connection between insulin with the pathophysiology of neurodegenerative diseases (AD and PD) and the current therapeutic approached mediated through insulin for management of neurodegenerative diseases. An extensive literature search was conducted using keywords “insulin”; “insulin resistance”; “Alzheimer’s disease”; “Parkinson’s disease” in public domains of Google scholar, PubMed, and ScienceDirect. Selected articles were used to construct this review. Studies have shown that impaired insulin signaling contributes to the accumulation of amyloid-β, neurofibrillary tangles, tau proteins and α-synuclein in the brain. Whereas, improvement in insulin signaling slows down the progression of cognitive decline. Various therapeutic approaches for altering the insulin function in the brain have been researched. Besides intranasal insulin, other therapeutics like PPAR-γ agonists, neurotrophins, stem cell therapy and insulin-like growth factor-1 are under investigation. Research has shown that insulin insensitivity in T2DM leads to neurodegeneration through mechanisms involving a variety of extracellular, membrane receptor, and intracellular signaling pathway disruptions. Some therapeutics, such as intranasal administration of insulin and neuroactive substances have shown promise but face problems related to genetic background, accessibility to the brain, and invasiveness of the procedures.

scholarly journals Trimethylamine N-Oxide (TMAO) links peripheral insulin resistance and cognitive deficiencies in a senescence accelerated mouse model

2021 ◽  
Author(s):  
Manuel H. Janeiro ◽  
Elena Puerta ◽  
Maria Lanz ◽  
Fermin I. Milagro ◽  
Maria J Ramirez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Insulin Signaling ◽  
Samp8 Mouse ◽  
Cognitive Deficiencies ◽  
Samp8 Mice ◽  
The Brain ◽  
Senescence Accelerated Mouse

It has been established that ageing is the major risk factor for cognitive deficiency or neurodegenerative diseases such as Alzheimer's disease (AD) and it is becoming increasingly evident that insulin resistance is another factor. Biological plausibility for a link between insulin resistance and dementia is relevant for understanding disease etiology, and to form bases for prevention efforts to decrease disease burden. The dysfunction of the insulin signaling system and glucose metabolism has been proposed to be responsible for brain aging. Normal insulin signaling in the brain is required to mediate growth, metabolic functions, and the survival of neurons and glia. Insulin receptors are densely expressed in the olfactory bulb, the cerebral cortex and the hippocampus and regulate neurotransmitter release and receptor recruitment. In normal elderly individuals, reduced glucose tolerance and decreased insulin levels in the aged brain are typically observed. Furthermore, insulin signaling is aberrantly activated in the AD brain, leading to non-responsive insulin receptor signaling. The senescence accelerated mouse (SAMP8) mouse was one of the accelerated senescence strains that spontaneously developed from breeding pairs of the AKR/J series. The SAMP8 mouse develops early learning and memory deficits (between 6 and 8 months) together with other characteristics similar to those seen in Alzheimer's disease. The present project proposes the investigation of the missing link between aging, insulin resistance and dementia. Peripheral but not central insulin resistance was found in SAMP8 mice accompanied by cognitive deficiencies. Furthermore, a marked peripheral inflammatory state (i.e. significantly higher adipose tissue TNF-[alpha]; and IL6 levels) were observed in SAMP8 mice, followed by neuroinflammation that could be due to a higher cytokine leaking into the brain across a aging-disrupted BBB. Moreover, aging-induced gut dysbiosis produces higher TMAO that could also contribute to the peripheral and central inflammatory tone as well as to the cognitive deficiencies observed in SAMP8 mice. All those alterations were reversed by DMB, a treatment inhibits the transformation of choline, carnitine and crotonobetaine, decreaseing TMAO levels. The ever-increasing incidence of neurodegenerative diseases not only limits the life quality of the affected individuals and their families but also poses an enormous demand on the societies. Thus, it is instrumental to pursue novel promising approaches to prevent and treat it at the highest possible speed to rapidly translate them to clinical practice. From this point of view, data obtained from this project will be instrumental to validate the principle approach of microbial dysbiosis and increased TMAO secretion as a key link between aging, insulin resistance and dementia. Collectively, the proposed experiments ideally integrate the aim to promote a novel approach to improve the lives of those suffering from cognitive disturbances.

scholarly journals Clinicotherapeutic Potential of Leptin in Alzheimer’s Disease and Parkinson’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Soumyabrata Munshi ◽  
Vineet Kumar Khemka ◽  
Kalpita Banerjee ◽  
Sasanka Chakrabarti
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Peptide Hormone ◽  
The Elderly ◽  
Clinical Associations ◽  
The Brain

Chronic neurodegenerative diseases are a group of devastating neurological disorders that result in significant morbidity and mortality in the elderly population worldwide. Recent researches have shown some interesting associations of the classical antiobesity hormone leptin with two most important neurodegenerative diseases—Alzheimer’s disease (AD) and Parkinson’s disease (PD). Although several clinical studies have found the procognitive and memory-enhancing role of this peptide hormone in leptin-deficient patients, surprisingly it has not been used in any clinical trials involving patients with developing or full-blown neurodegenerative conditions. This review article is an attempt to bring together the existing information about the clinical associations of leptin with AD and PD. It starts with the basic understanding of leptin action in the brain and its derangements in these diseases and eventually discusses the potential of this hormone as a neuroprotective agent in clinical scenario.

scholarly journals The Role of Salivary Biomarkers in the Early Diagnosis of Alzheimer’s Disease and Parkinson’s Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 371
Author(s):  
Patrycja Pawlik ◽  
Katarzyna Błochowiak
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Early Diagnosis ◽  
Neurodegenerative Diseases ◽  
Diagnostic Tool ◽  
Clinical Symptoms ◽  
Early Screening ◽  
Salivary Biomarkers

Many neurodegenerative diseases present with progressive neuronal degeneration, which can lead to cognitive and motor impairment. Early screening and diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are necessary to begin treatment before the onset of clinical symptoms and slow down the progression of the disease. Biomarkers have shown great potential as a diagnostic tool in the early diagnosis of many diseases, including AD and PD. However, screening for these biomarkers usually includes invasive, complex and expensive methods such as cerebrospinal fluid (CSF) sampling through a lumbar puncture. Researchers are continuously seeking to find a simpler and more reliable diagnostic tool that would be less invasive than CSF sampling. Saliva has been studied as a potential biological fluid that could be used in the diagnosis and early screening of neurodegenerative diseases. This review aims to provide an insight into the current literature concerning salivary biomarkers used in the diagnosis of AD and PD. The most commonly studied salivary biomarkers in AD are β-amyloid1-42/1-40 and TAU protein, as well as α-synuclein and protein deglycase (DJ-1) in PD. Studies continue to be conducted on this subject and researchers are attempting to find correlations between specific biomarkers and early clinical symptoms, which could be key in creating new treatments for patients before the onset of symptoms.

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.

scholarly journals The Role of Long Noncoding RNAs in Diabetic Alzheimer’s Disease

2018 ◽  
Vol 7 (11) ◽  
pp. 461 ◽  
Author(s):  
Young-Kook Kim ◽  
Juhyun Song
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Glucose Dysregulation ◽  
Near Future ◽  
The Brain

Long noncoding RNAs (lncRNAs) are involved in diverse physiological and pathological processes by modulating gene expression. They have been found to be dysregulated in the brain and cerebrospinal fluid of patients with neurodegenerative diseases, and are considered promising therapeutic targets for treatment. Among the various neurodegenerative diseases, diabetic Alzheimer’s disease (AD) has been recently emerging as an important issue due to several unexpected reports suggesting that metabolic issues in the brain, such as insulin resistance and glucose dysregulation, could be important risk factors for AD. To facilitate understanding of the role of lncRNAs in this field, here we review recent studies on lncRNAs in AD and diabetes, and summarize them with different categories associated with the pathogenesis of the diseases including neurogenesis, synaptic dysfunction, amyloid beta accumulation, neuroinflammation, insulin resistance, and glucose dysregulation. It is essential to understand the role of lncRNAs in the pathogenesis of diabetic AD from various perspectives for therapeutic utilization of lncRNAs in the near future.

scholarly journals Occupational Exposures and Neurodegenerative Diseases—A Systematic Literature Review and Meta-Analyses

2019 ◽  
Vol 16 (3) ◽  
pp. 337 ◽  
Author(s):  
Lars-Gunnar Gunnarsson ◽  
Lennart Bodin
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Occupational Exposure ◽  
Neurodegenerative Diseases ◽  
Meta Analysis ◽  
Occupational Exposures ◽  
Increased Risk ◽  
Meta Analyses

Objectives: To carry out an integrated and stratified meta-analysis on occupational exposure to electromagnetic fields (EMFs), metals and pesticides and its effects on amyotrophic lateral sclerosis (ALS) and Parkinson’s and Alzheimer’s disease, and investigate the possibility of publication bias. Methods: In the current study, we updated our recently published meta-analyses on occupational exposures in relation to ALS, Alzheimer’s and Parkinson’s disease. Based on 66 original publications of good scientific epidemiological standard, according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines, we analysed subgroups by carrying out stratified meta-analyses on publication year, statistical precision of the relative risk (RR) estimates, inspection of the funnel plots and test of bias. Results: Based on 19 studies the weighted RR for occupational exposure to EMFs was 1.26 (95% confidence interval (CI) 1.07–1.50) for ALS, 1.33 (95% CI 1.07–1.64) for Alzheimer’s disease and 1.02 (95% CI 0.83–1.26) for Parkinson’s disease. Thirty-one studies concerned occupational exposure to pesticides and the weighted RR was 1.35 (95% CI 1.02–1.79) for ALS, 1.50 (95% CI 0.98–2.29) for Alzheimer’s disease and 1.66 (95% CI 1.42–1.94) for Parkinson’s disease. Finally, 14 studies concerned occupational exposure to metals and only exposure to lead (five studies) involved an elevated risk for ALS or Parkinson’s disease and the weighted RR was 1.57 (95% CI 1.11–2.20). The weighted RR for all the non-lead exposures was 0.97 (95% CI 0.88–1.06). Conclusions: Exposure to pesticides increased the risk of getting the mentioned neurodegenerative diseases by at least 50%. Exposure to lead was only studied for ALS and Parkinson’s disease and involved 50% increased risk. Occupational exposure to EMFs seemed to involve some 10% increase in risk for ALS and Alzheimer’s disease only.

scholarly journals The relationship of diabetes mellitus with Alzheimer’s disease: a literature review

2021 ◽  
Author(s):  
Fábio Dias Nogueira ◽  
Ana Klara Rodrigues Alves ◽  
Barbara Beatriz Lira da Silva ◽  
Ana Kamila Rodrigues Alves ◽  
Marlilia Moura Coelho Sousa ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Potential Link ◽  
The Central Nervous System ◽  
Gsk 3Β ◽  
Type 3 ◽  
The Brain

Introduction: Alzheimer’s disease (AD) is closely related to diabetes mellitus (DM), and AD is also considered to be type 3 diabetes (T3D). Glycogen synthase kinase-3β (GSK-3β) may be the potential link between DM and AD. GSK-3β is one of the main factors that lead to insulin deficiency and insulin resistance, and insulin resistance is a characteristic of the development of DM. In AD, GSK-3β plays an important role in hyperphosphorylation of the tau protein (tau) associated with microtubules, which is one of the pathological features in AD. Objective: To analyze DM as a factor for the development of AD. METHODOLOGY: This is an integrative review of the literature, which is a construction of a comprehensive analysis of the literature with pre-defined steps, carried out through PubMed, 1.501 articles were found, of which 10 were selected, through the simultaneous crossing between the descriptors “Diabetes mellitus”, “Alzheimer “. Articles written in Portuguese and English published between 2016 and 2021 were inserted. Results: DM associated with insulin resistance affects psychomotor efficiency, attention, learning memory, mental flexibility, speed and executive function of the brain, thus being an independent risk factor for cognitive impairment and damage to the central nervous system, hyperglycemia, which can cause increased oxidative stress leading to progressive functional and structural abnormalities in the brain. Conclusion:The risk of dementia in patients with DM is higher than in nondiabetic patients and it is also well known that DM2 / insulin resistance is involved in AD.

Neurodegenerative diseases and Flavonoids: Special reference to kaempferol

2021 ◽  
Vol 20 ◽  
Author(s):  
Rahul ◽  
Yasir Hasan Siddique
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neuroprotective Effects ◽  
Major Health Problem ◽  
Beneficial Effects

: Neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington’s disease, Multiple Sclerosis and Ischemic stroke have become a major health problem worldwide. Pre-clinical studies have demonstrated the beneficial effects of flavonoids on neurodegenerative diseases and suggesting them to be used as therapeutic agents. Kaempferol is found in many plants such as tea, beans, broccoli,strawberriesand has neuroprotective effects against the development of many neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and Huntington's disease. The present study summarizesthe neuroprotective effects of kaempferol in various models of neurodegenerative diseases. Kaempferol delays the initiation as well as the progression of neurodegenerative disorders by acting as a scavenger of free radicals and preserving the activity of various antioxidant enzymes. Kaempferolcan crossthe blood-brain barrier (BBB), and therefore results inan enhanced protective effect. The multi-target property of kaempferol makes it a potential dietary supplement in preventing and treating neurodegenerative diseases.

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