Effects of Ketogenic Diet on Neuroinflammation in Neurodegenerative Diseases

Aging and Disease, Journal Year: 2022, Volume and Issue: 13(4), P. 1146 - 1146

Published: Jan. 1, 2022

The ketogenic diet (KD) is a low-carbohydrate, high-fat and adequate-protein diet. As mimicking fasting, it triggers the production of ketone bodies (KBs) brings body into state ketosis. Recent accumulating studies on humans animal models have shown that KD beneficial to neurodegenerative diseases through modulating central peripheral metabolism, mitochondrial function, inflammation, oxidative stress, autophagy, gut microbiome. Complicated interplay microbiome, other mechanisms can regulate neuroinflammation in by activating multiple molecular cellular pathways. In this review, we detail physiological basis KD, its functions regulating neuroinflammation, protective role normal brain aging diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS), Huntington’s (HD). We aimed elucidate underlying neuroinflammatory therapies provide novel insights their application for prevention treatment.

Language: Английский

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The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer’s disease

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 17, 2022

Since type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer’s disease (AD) and both have the same pathogenesis (e.g., insulin resistance), drugs used to treat T2DM been gradually found reduce progression of AD in models. Of these drugs, glucagon-like peptide 1 receptor (GLP-1R) agonists are more effective fewer side effects. GLP-1R reducing neuroinflammation oxidative stress, neurotrophic effects, decreasing Aβ deposition tau hyperphosphorylation models, which may be potential drug treatment AD. However, this needs verified by further clinical trials. This study aims summarize current information on mechanisms effects

Language: Английский

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Gastrodin From Gastrodia elata Enhances Cognitive Function and Neuroprotection of AD Mice via the Regulation of Gut Microbiota Composition and Inhibition of Neuron Inflammation

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: June 2, 2022

Gastrodin (Gas) is known to exhibit neuroprotective effects in Alzheimer's disease (AD). However, the detailed mechanism of action still unclear. In present study, we focused on microbiome-gut-brain axis investigate Gas using a D-galactose (Dgal)-induced AD model. reversed memory dysfunction Dgal-administered mice. Neurons cerebral cortex and hippocampus were reduced group, decrease neurons was suppressed 90 210 mg/kg treatment groups. 16S rRNA sequence analysis carried out explore composition gut microbiota fecal samples had positive correlation with Firmicutes negative Cyanobacteria, Proteobacteria, Deferribaceters. Importantly, LPS proinflammatory cytokines brain increased mice, but these parameters recovered normal levels after oral administration Gas. To determine whether microbiota-gut-brain involved effect Gas, mice given antibiotic cocktail before during trial period The partially eliminated by changing microbiome composition. These results indicated that improves mouse model via partly targeting mitigating neuron inflammation.

Language: Английский

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The neuroprotective effects of intermittent fasting on brain aging and neurodegenerative diseases via regulating mitochondrial function

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 182, P. 206 - 218

Published: Feb. 24, 2022

Language: Английский

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Preclinical Models for Alzheimer’s Disease: Past, Present, and Future Approaches

ACS Omega, Journal Year: 2022, Volume and Issue: 7(51), P. 47504 - 47517

Published: Dec. 13, 2022

A robust preclinical disease model is a primary requirement to understand the underlying mechanisms, signaling pathways, and drug screening for human diseases. Although various models are available several diseases, clinical Alzheimer's (AD) remain underdeveloped inaccurate. The pathophysiology of AD mainly includes presence amyloid plaques neurofibrillary tangles (NFT). Furthermore, neuroinflammation free radical generation also contribute AD. Currently, there wide gap in scientific approaches preventing progression. Most drugs limited symptomatic relief improve deteriorating cognitive functions. To mimic pathogenesis AD, animal like 3XTg-AD 5XFAD primarily used mice therapeutics. Animal include intracerebroventricular-streptozotocin (ICV-STZ), beta-induced, colchicine-induced, etc., focusing on parameters such as decline dementia. Unfortunately, translational rate potential candidates trials poor due limitations imitating pathology models. Therefore, possess modeling. This paper presents an outline that critically assesses applicability current modeling Also, we attempted provide key suggestions best-fit evaluate therapies, which might therapy translation from studies patients with

Language: Английский

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Cognitive dysfunction in diabetes: abnormal glucose metabolic regulation in the brain

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: June 16, 2023

Cognitive dysfunction is increasingly recognized as a complication and comorbidity of diabetes, supported by evidence abnormal brain structure function. Although few mechanistic metabolic studies have shown clear pathophysiological links between diabetes cognitive dysfunction, there are several plausible ways in which this connection may occur. Since, functions require constant supply glucose an energy source, the be more susceptible to abnormalities metabolism. Glucose under diabetic conditions play important role affecting transport reducing These changes, along with oxidative stress, inflammation, mitochondrial other factors, can affect synaptic transmission, neural plasticity, ultimately lead impaired neuronal Insulin signal triggers intracellular transduction that regulates resistance, one hallmark has also been linked cerebral metabolism brain. In review, we conclude critical alterations underlying (DCD), associated multiple pathogenic factors such others. Brain insulin resistance highly emphasized characterized mechanism DCD.

Language: Английский

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Insulin signaling and its application

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 17, 2023

The discovery of insulin in 1921 introduced a new branch research into activity and resistance. Many discoveries this field have been applied to diagnosing treating diseases related In mini-review, the authors attempt synthesize updated unravel mechanisms inform development novel applications. Firstly, we depict signaling pathway explain physiology action starting at receptor sites downstream pathway. Based on this, next part will analyze resistance with two major provenances: defects caused by receptors due extra-receptor causes, but study, focus post-receptor causes. Finally, discuss recent applications including (obesity, cardiovascular disease, Alzheimer's cancer) potential treatment those based mechanisms.

Language: Английский

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Migraine, Brain Glucose Metabolism and the “Neuroenergetic” Hypothesis: A Scoping Review

Journal of Pain, Journal Year: 2022, Volume and Issue: 23(8), P. 1294 - 1317

Published: March 14, 2022

Increasing evidence suggests that migraine may be the result of an impaired brain glucose metabolism. Several studies have reported mitochondrial dysfunction, metabolism and gray matter volume reduction in specific areas migraineurs. Furthermore, peripheral insulin resistance, a condition demonstrated several studies, extend to brain, leading resistance. This has been proven downregulate receptors, both astrocytes neurons, triggering uptake glycogen synthesis, mainly during high metabolic demand. scoping review examines clinical, epidemiologic pathophysiologic data supporting hypothesis abnormalities generate mismatch between brain's energy reserve expenditure, attacks. Moreover, alteration homeostasis could chronic deficit promoting chronification. Lastly, resistance link with its comorbidities, like obesity, depression, cognitive impairment cerebrovascular diseases.PerspectiveAlthough additional experimental are needed support this novel “neuroenergetic” hypothesis, migraineurs unravel pathophysiological mechanisms disease, explaining chronification connecting comorbidities. Therefore, elucidate potential approaches for treatment.

Language: Английский

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Potential Role of Glucagon-like Peptide-1 Receptor Agonists in the Treatment of Cognitive Decline and Dementia in Diabetes Mellitus

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11301 - 11301

Published: July 11, 2023

Dementia is a permanent illness characterized by mental instability, memory loss, and cognitive decline. Many studies have demonstrated an association between diabetes dysfunction that proceeds in three steps, namely, diabetes-associated decrements, mild impairment (MCI; both non-amnesic MCI amnesic MCI), dementia [both vascular Alzheimer’s disease (AD)]. Based on this association, has been designated as type 3 mellitus. The underlying mechanisms comprise insulin resistance, inflammation, lipid abnormalities, oxidative stress, mitochondrial dysfunction, glycated end-products autophagy. Moreover, insulin-like growth factor-1 (IGF-1) to be involved. Insulin the brain neuroprotective role alters skills alteration of signaling determines beta-amyloid (Aβ) accumulation, turn promoting resistance. In complex mechanism, other triggers include hyperglycemia-induced overproduction reactive oxygen species (ROS) inflammatory cytokines, which result neuroinflammation, suggesting antidiabetic drugs may potential treatments protect against AD. Among these, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are most attractive due their actions synaptic plasticity, cognition cell survival. present review summarizes significant data concerning pathophysiological pharmacological dementia.

Language: Английский

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Phytochemicals targeting Alzheimer's disease via the AMP-activated protein kinase pathway, effects, and mechanisms of action

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116373 - 116373

Published: March 4, 2024

Alzheimer's disease (AD), characterized by cognitive dysfunction and other behavioral abnormalities, is a progressive neurodegenerative that occurs due to aging. Currently, effective drugs mitigate or treat AD remain unavailable. associated with several abnormalities in neuronal energy metabolism, such as decreased glucose uptake, mitochondrial dysfunction, defects cholesterol metabolism. Amp-activated protein kinase (AMPK) an important serine/threonine regulates the status of cells. AMPK widely present eukaryotic cells can sense regulate metabolism maintain supply demand balance, making it promising target for metabolism-based therapy. Therefore, this review aimed discuss molecular mechanism pathogenesis provide theoretical basis development new anti-AD drugs. To mechanisms phytochemicals treatment via pathway regulation, we searched PubMed, Google Scholar, Web Science, Embase databases using specific keywords related September 2023. Phytochemicals activate exert therapeutic effects AD. The these include inhibiting Aβ aggregation, preventing Tau hyperphosphorylation, inflammatory response glial activation, promoting autophagy, suppressing anti-oxidative stress. Additionally, AMPK-related pathways are involved mechanism, including AMPK/CaMKKβ/mTOR, AMPK/SIRT1/PGC-1α, AMPK/NF-κB/NLRP3, AMPK/mTOR, PERK/eIF2α pathways. Notably, urolithin A, artemisinin, justicidin berberine, stigmasterol, arctigenin, rutaecarpine agonists effects. Several may have potential applications treatment. Overall, phytochemical-based overcome barriers diseases.

Language: Английский

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