A Potential Link Between Visceral Obesity and Risk of Alzheimer’s Disease

Neurochemical Research, Год журнала: 2022, Номер 48(3), С. 745 - 766

Опубликована: Ноя. 21, 2022

Язык: Английский

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Significance of Brain Glucose Hypometabolism, Altered Insulin Signal Transduction, and Insulin Resistance in Several Neurological Diseases

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Май 9, 2022

Several neurological diseases share pathological alterations, even though they differ in their etiology. Neuroinflammation, altered brain glucose metabolism, oxidative stress, mitochondrial dysfunction and amyloidosis are biological events found those disorders. Altered insulin-mediated signaling hypometabolism characteristic signs observed the brains of patients with certain diseases, but also others such as type 2 diabetes mellitus vascular diseases. Thus, significant reductions insulin receptor autophosphorylation Akt kinase activity, increased GSK-3 activity resistance, have been reported these contributing to decline cognitive function. Supporting this relationship is fact that nasal hippocampal administration has improve Additionally, precedes unmistakable clinical manifestations some by years, which may become a useful early biomarker. Deficiencies major pathways energy metabolism several supports hypothesis metabolic background. This review remarks on significance alterations keystone common pathogenic substrates for highlighting new potential targets.

Язык: Английский

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Insulin and Its Key Role for Mitochondrial Function/Dysfunction and Quality Control: A Shared Link between Dysmetabolism and Neurodegeneration

Biology, Год журнала: 2022, Номер 11(6), С. 943 - 943

Опубликована: Июнь 20, 2022

Insulin was discovered and isolated from the beta cells of pancreatic islets dogs is associated with regulation peripheral glucose homeostasis. produced in brain related to synaptic plasticity memory. Defective insulin signaling plays a role dysfunction, such as neurodegenerative disease. Growing evidence suggests link between metabolic disorders, diabetes obesity, diseases, especially Alzheimer’s disease (AD). This association due common state resistance (IR) mitochondrial dysfunction. review takes journey into past summarize what known about physiological pathological tissues brain. Then, it will land present analyze on health effects diseases that are IR-dependent. Specifically, we focus our attention quality control mitochondria (MQC), dynamics, biogenesis, selective autophagy (mitophagy), healthy altered cases. Finally, this be projected toward future by examining most promising treatments target cure disorders.

Язык: Английский

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Insulin resistance in ischemic stroke: Mechanisms and therapeutic approaches

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Дек. 15, 2022

The pathological condition of insulin resistance prevents the neuroprotective effects insulin. Numerous studies have demonstrated that resistance, as an independent risk factor for ischemic stroke, accelerates formation thrombosis and promotes development atherosclerosis, both which are major mechanisms stroke. Additionally, negatively affects prognosis patients with stroke regardless whether patient has diabetes, but not well studied. We explored association between primary brain injury in (inflammation, oxidative stress, neuronal damage), looking potential causes poor due to resistance. Furthermore, we summarize therapeutic approaches propose new directions clinically improving

Язык: Английский

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The Role of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) in Diabetes-Related Neurodegenerative Diseases

Drug Design Development and Therapy, Год журнала: 2022, Номер Volume 16, С. 665 - 684

Опубликована: Март 1, 2022

Abstract: Recent clinical guidelines have emphasized the importance of screening for cognitive impairment in older adults with diabetes, however, there is still a lack understanding about drug therapy. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are widely used treatment type 2 diabetes and potential applications may include obesity as well adjunctive mellitus combination insulin. Growing evidence suggests that GLP-1 RA has to treat neurodegenerative diseases, particularly diabetes-related Alzheimer's disease (AD) Parkinson's (PD). Here, we review molecular mechanisms neuroprotective effects degenerative including AD PD, their effects. Keywords: glucagon-like peptide-1, mellitus, disease, cognition

Язык: Английский

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Inside the diabetic brain: Insulin resistance and molecular mechanism associated with cognitive impairment and its possible therapeutic strategies

Pharmacological Research, Год журнала: 2022, Номер 182, С. 106358 - 106358

Опубликована: Июль 18, 2022

Язык: Английский

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How Can Insulin Resistance Cause Alzheimer’s Disease?

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 3506 - 3506

Опубликована: Фев. 9, 2023

Alzheimer's disease (AD) is a neurodegenerative disorder associated with cognitive decline. Despite worldwide efforts to find cure, no proper treatment has been developed yet, and the only effective countermeasure prevent progression by early diagnosis. The reason why new drug candidates fail show therapeutic effects in clinical studies may be due misunderstanding cause of AD. Regarding AD, most widely known amyloid cascade hypothesis, which deposition beta hyperphosphorylated tau cause. However, many hypotheses were suggested. Among them, based on preclinical evidence supporting connection between AD diabetes, insulin resistance pointed out as an important factor development Therefore, reviewing pathophysiological background brain metabolic insufficiency leading pathology, we will discuss how can

Язык: Английский

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The Molecular Mechanisms of the Relationship between Insulin Resistance and Parkinson’s Disease Pathogenesis

Nutrients, Год журнала: 2023, Номер 15(16), С. 3585 - 3585

Опубликована: Авг. 15, 2023

Parkinson’s disease (PD) is a degenerative condition resulting from the loss of dopaminergic neurons. This neuronal leads to motor and non-motor neurological symptoms. Most PD cases are idiopathic, no cure available. Recently, it has been proposed that insulin resistance (IR) could be central factor in development. IR associated with neuropathological features like α-synuclein aggregation, loss, neuroinflammation, mitochondrial dysfunction, autophagy. These related impaired metabolism, death, aggravation Moreover, pharmacological options involve signaling improvement non-dopaminergic strategies have under drugs prevent metabolic pathways involved damage. All these approaches improve outcomes. Also, new biomarker identification may allow for an earlier diagnosis high-risk individuals. review describes main implicated development involving IR. presents several therapeutic directed at used treatment. The understanding molecular mechanisms neurodegenerative enhance diagnosis.

Язык: Английский

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Type 2 Diabetes and Alzheimer’s Disease: The Emerging Role of Cellular Lipotoxicity

Biomolecules, Год журнала: 2023, Номер 13(1), С. 183 - 183

Опубликована: Янв. 16, 2023

Type 2 diabetes (T2D) and Alzheimer’s diseases (AD) represent major health issues that have reached alarming levels in the last decades. Although growing evidence demonstrates AD is a significant comorbidity of T2D, there ~1.4–2-fold increase risk developing among T2D patients, involvement possible common triggers pathogenesis these two remains largely unknown. Of note, recent mechanistic insights suggest lipotoxicity could missing ring pathogenetic mechanisms linking to AD. Indeed, obesity, which represents main cause lipotoxicity, has been recognized as factor for both pathological conditions. Lipotoxicity can lead inflammation, insulin resistance, oxidative stress, ceramide amyloid accumulation, endoplasmic reticulum ferroptosis, autophagy, are shared biological events In current review, we try provide critical comprehensive view molecular pathways activated by AD, attempting summarize how drive future research open way new therapeutic perspectives.

Язык: Английский

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Diet’s Role in Modifying Risk of Alzheimer’s Disease: History and Present Understanding

Journal of Alzheimer s Disease, Год журнала: 2023, Номер 96(4), С. 1353 - 1382

Опубликована: Ноя. 7, 2023

Diet is an important nonpharmacological risk-modifying factor for Alzheimer's disease (AD). The approaches used here to assess diet's role in the risk of AD include multi-country ecological studies, prospective and cross-sectional observational laboratory studies. Ecological studies have identified fat, meat, obesity from high-energy diets as factors reported that rates peak about 15-20 years after national dietary changes. Observational compared Western pattern with those Dietary Approaches Stop Hypertension (DASH), Mediterranean (MedDi), Mediterranean-DASH Intervention Neurodegenerative Delay (MIND) diets. Those including higher consumption saturated total fats, ultraprocessed foods a lower fruits, legumes, nuts, omega-3 fatty acids, vegetables, whole grains. Diet-induced associated significant inflammation, insulin resistance, oxidative stress, elevated homocysteine, advanced glycation end products, trimethylamine N-oxide. molecular mechanisms by which bioactive components specific affect are discussed. Given most countries' entrenched food supply systems, upward trends would be hard reverse. However, people willing able, low-animal product diet plenty anti-inflammatory, low-glycemic load may helpful.

Язык: Английский

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