Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 19(9), P. 609 - 633

Published: July 24, 2020

Language: Английский

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Obesity ‑ a risk factor for increased COVID‑19 prevalence, severity and lethality (Review)

Molecular Medicine Reports, Journal Year: 2020, Volume and Issue: 22(1), P. 9 - 19

Published: May 5, 2020

Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are a group of viruses that cause infections in the human respiratory tract, which can be characterized clinically from mild to fatal. The severe acute syndrome coronavirus 2 (SARS‑CoV‑2) is virus responsible. global spread COVID‑19 described as worst pandemic humanity last century. To date, has infected more than 3,000,000 people worldwide and killed 200,000 people. All age groups virus, but serious symptoms possibly result death observed older those with underlying medical conditions such cardiovascular pulmonary disease. Novel data report even negative prognosis for obese patients. A growing body evidence connects obesity number mechanisms immune system activity attenuation chronic inflammation implicated. Lipid peroxidation creates reactive lipid aldehydes patient metabolic disorder will affect its prognosis. Finally, pregnancy‑associated needs studied further connection this infection could pose high risk both pregnant women fetus.

Language: Английский

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Obesity as a Risk Factor for Dementia and Alzheimer’s Disease: The Role of Leptin

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 5202 - 5202

Published: May 6, 2022

Obesity is a growing worldwide health problem, affecting many people due to excessive saturated fat consumption, lack of exercise, or sedentary lifestyle. Leptin an adipokine secreted by adipose tissue that increases in obesity and has central actions not only at the hypothalamic level but also other regions nuclei nervous system (CNS) such as cerebral cortex hippocampus. These express long form leptin receptor LepRb, which unique capable transmitting complete signaling, are first be affected chronic neurocognitive deficits, mild cognitive impairment (MCI) Alzheimer’s Disease (AD). In this review, we discuss different resistance mechanisms could implicated increasing risk developing AD, frequently associated with obesity, low-grade inflammatory state, considered factor for AD. Key players SOCS3, PTP1B, TCPTP whose signalling related inflammation worsened However, some data controversial, it necessary further investigate underlying AD-causing pathological processes how altered affects processes.

Language: Английский

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Cardiometabolic risk factors and neurodegeneration: a review of the mechanisms underlying diabetes, obesity and hypertension in Alzheimer’s disease

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2024, Volume and Issue: 95(6), P. 581 - 589

Published: Jan. 30, 2024

A growing body of evidence suggests that cardiometabolic risk factors play a significant role in Alzheimer’s disease (AD). Diabetes, obesity and hypertension are highly prevalent can accelerate neurodegeneration perpetuate the burden AD. Insulin resistance enzymes including insulin degrading implicated AD where breakdown is prioritised over amyloid-β. Leptin inflammation demonstrated by higher plasma central nervous system levels interleukin-6 (IL-6), IL-1β tumour necrosis factor-α, mechanisms connecting diabetes with has been shown to ameliorate pathology enhance long-term potentiation hippocampal-dependent cognitive function. The renin-aldosterone angiotensin system, involved hypertension, associated neurotoxic reactive oxygen species, binds specific angiotensin-1 receptors hippocampus cerebral cortex. This review aims consolidate behind putative processes stimulated obesity, which leads increased risk. We focus on how novel knowledge be applied clinically facilitate recognition efficacious treatment strategies for

Language: Английский

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Body and mind: how obesity triggers neuropsychiatric and neurodegenerative disorders

Frontiers in Psychiatry, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

Obesity has emerged as a significant health concern, particularly affecting young people worldwide.Its prevalence extends beyond Westernized countries and been projected to rise from 107.7 million obese children adolescents in 2015 254 by 2030 (1). This metabolic disorder poses severe consequences for healthcare systems globally, childhood obesity often persists into adulthood (2). Unlike other diseases, is pathological condition that renders individuals more susceptible various disorders, including syndrome, cardiovascular disease, nonalcoholic fatty liver cancer (3).Metabolic dysfunctions disrupt the structural functional of humans, central nervous system (CNS) (4). The hypothalamus, pivotal region situated between CNS periphery, serves control center energy homeostasis, body temperature, food intake, essential functions (5). Consuming diet high calories, carbohydrates lipids, triggers vicious cycle hyperactivation immune cells neuroinflammatory mediators within resulting widespread effects (6). Consequently, alterations this key brain led impairments all related neuronal circuits areas, mesolimbic dopamine (DA) system, hippocampus, nucleus accumbens, striatum, cortex, which are primarily associated with such cognition mood regulation.The gut microbiota plays role pathophysiology neuropsychiatric neurodegenerative context obesity. gut-brain axis mediates relationship (7). Obesity-induced peripheral influence function enhancing neuroinflammation, altering neurotransmitter synthesis, impairing insulin signaling These mechanisms have elevated risks depression, anxiety, cognitive decline, diseases (8). Specifically, Proteobacteria Cyanobacteria overrepresented patients (9,10). dysregulation metabolites these bacteria may contribute systemic inflammation oxidative damage, indirectly pathways relevant (11,12).Obesity disorders intricately interconnected, their share numerous characteristics (13). At level, obesity-related detrimental factors compromised integrity blood-brain barrier (BBB), prevents entry substances (14). BBB sophisticated highly specialized biological construct, characterized its selective permeability protective CNS. leads BBB, increased permeability, altered transport mechanisms, inflammatory responses Consistently, our findings indicate disruption induced high-fat (HFD) evidenced albumin extravasation hippocampus mice, represents critical mechanism pathogenesis (15). In condition, signals via gut-microbiotabrain can impact activity, both negatively positively metainflammation, levels pro-inflammatory mediators, activates astrogliosis microgliosis, leading neuroinflammation (16). microglia, resident CNS, (17). Under normal conditions, microglia maintain homeostasis regulating synaptic pruning clearing cellular debris. However, response chronic stress or inflammation, become activated release lead neurotoxicity (18). blocks machinery responsible neurogenesis, process renewal (19). Indeed, reduce neurogenesis suppressing stem cell proliferation, increasing apoptosis progenitor cells, decreasing survival newly developing neurons integration existing (20). Furthermore, long-term consumption Western-style HFD, low fiber content, substantial reduction short-chain acids, endogenous molecules notable anti-inflammatory neurogenesis-promoting properties (21). Our studies demonstrated HFD feeding depressive-and anxiety-like behavior intestinal dysbiosis, proliferation inflammatory-related microbes, alteration tryptophan metabolite pathway (22). production toxic tryptophan, quinolinic kynurenic acid, severally (23). neurobiological encompass reward circuitry, diminished serotonin (5-HT) DA levels, augmented hypothalamic-pituitary-adrenal (HPA) component body's (24). particular, known balance neurotransmitters regulation, 5-HT gammaaminobutyric acid (GABA). Elevated interleukin (IL)-6 tumor necrosis factor (TNF)-α serotonergic GABAergic systems, exacerbate symptoms (25). conditions serve etiological basis depressive anxiety phenotypes.Given growing intricate recent evidence also highlights shared mechanistic targets two conditions. For instance, peroxisome proliferator-activated receptor (PPAR)-α, whose lipid metabolism tissues well-established clinical therapy, recently recognized an tranquilizer caused dysmetabolism (26). PPAR-α widely distributed across amygdala, prefrontal thalamic nuclei, ventral tegmental area (VTA), basal ganglia (27). Moreover, research Jiang et al. (28) agonist WY14643 ameliorated depressive-like behaviors effect attributed activation Brain-Derived Neurotrophic Factor pathway.Neurodegenerative increasingly complex, bidirectional (29). Obesity, midlife, risk several Alzheimer's disease (AD), Parkinson's (PD), forms decline (30). correlation mediated combination metabolic, inflammatory, hormonal affect (31). resistance, changes (leptin adipokines), mitochondrial dysfunction, (32). Metainflammation, feature many dysmetabolism, impairs Neuroinflammation, turn, accelerates damage contributes progression. increases free radicals decreases antioxidant defenses, (33). process, coupled impaired function, damages structures, proteins, DNA, accelerating degeneration (34).Emerging underscores obesity, etiology AD, even if aging primary AD (35). Therefore, significantly correlates dysfunction (36). context, excessive weight processes derangements increase amyloid β (Aβ) accumulation (37). connection Aβ deposition; low-grade state, reactive oxygen species (38). (39). HFD-linked observed induce impair impacting (40).Notably, VTA, involved function.Different types HFDs alter potentially perceptions intake (41).Insulin influences transporter establishing outcomes (42). appears involve expression dopamine-degrading enzymes MAO-A MAO-B, reduces (43).Furthermore, microglial progression (44). interplay implies not only but through involving adipose tissue.While PD traditionally genetic environmental toxins, emerging indicates development (29).Specifically, suggested later life. mass index range at midlife exhibited higher likelihood years (45).Obesity linked worsening motor non-motor (46). It causing stiffness, flexibility, hindering physical already challenge PD. Additionally, older adults, be vascular health, worsen (47). during adipocytes cytokines TNF-α, IL-6, C-reactive protein (48).Lipid overnutrition subsequent metainflammation direct on brain, exacerbating player As it dopaminergic neurons, crucial (49). Since neurotoxic promote obesity-induced further activation, (50).At molecular regulate DA, contributing onset (51). Notably, leptin, produced adipocytes, regulation brain's (52). Research suggests leptin hallmark signal transduction, (53).The purpose opinion draw attention obesity-driven investigating how address "pandemic wellness." Identifying causal interrelationships comorbidities, although complex task, prevent counteract gluco-lipid dysmetabolism. scientific community made progress understanding pathogenic (Figure 1), there still much accomplish. contemplating possibly targeting due could innovative therapeutic strategies emphasizing necessity comprehensive approach takes account disorders.

Language: Английский

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Association of diet and headache

The Journal of Headache and Pain, Journal Year: 2019, Volume and Issue: 20(1)

Published: Nov. 14, 2019

Abstract The global prevalence of migraine as a primary headache has been estimated 14.4% in both sexes. Migraine ranked the highest contributor to disability under 50 years old population world. Extensive research conducted order clarify pathological mechanisms migraine. Although uncertainties remains, it indicated that vascular dysfunction, cortical spreading depression (CSD), activation trigeminovascular pathway, pro-inflammatory and oxidative state may play putative role pain generation. Knowledge about pathophysiological should be integrated into multimodal treatment approach increase quality life patients. With respect this, within integrative health studies growing interest pertains dietary interventions. number concerning effects diet on headache/migraine is not yet very large, current article will review available evidence this area. All publications interventions up May 2019 were included present through PubMed/MEDLINE ScienceDirect database search. According findings, Ketogenic modified Atkins are thought neuroprotection, improving mitochondrial function energy metabolism, compensating serotoninergic decreasing calcitonin gene-related peptide (CGRP) level suppressing neuro-inflammation. It can also speculated prescription low glycemic promising control attenuating inflammatory state. Moreover, obesity headaches including could attributed each other like inflammation, irregular hypothalamic function. Thereby, applying strategies for weight loss ameliorate headache/migraine. Another important intervention might effective improvement related balance between intake essential fatty acids, omega-6 omega-3 which affect responses, platelet regulation tone. Regarding elimination diets, appears targeted these diets patients with food sensitivities prevention. Taken together, approaches considered prophylaxis include obese patients, ketogenic low-calorie reducing increasing acid intakes.

Language: Английский

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The role of innate immunity in Alzheimer's disease

Immunological Reviews, Journal Year: 2020, Volume and Issue: 297(1), P. 225 - 246

Published: June 26, 2020

Abstract The amyloid hypothesis has dominated Alzheimer's disease (AD) research for almost 30 years. This hinges on the predominant clinical role of beta (Aβ) peptide in propagating neurofibrillary tangles (NFTs) and eventual cognitive impairment AD. Recent AD field identified brain‐resident macrophages, known as microglia, their receptors integral regulators both initiation propagation inflammation, Aβ accumulation, neuronal loss, memory decline Emerging studies have also begun to reveal critical roles distinct innate immune pathways pathogenesis, which led great interest harnessing response a therapeutic strategy treat In this review, we will highlight recent advancements our understanding immunity inflammation onset progression. Additionally, there been mounting evidence suggesting pivotal contributions environmental factors lifestyle choices pathogenesis. Therefore, discuss findings, that many these risk influence progression via modulation microglia responses.

Language: Английский

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The Novel Perspectives of Adipokines on Brain Health

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(22), P. 5638 - 5638

Published: Nov. 11, 2019

First seen as a fat-storage tissue, the adipose tissue is considered critical player in endocrine system. Precisely, can produce an array of bioactive factors, including cytokines, lipids, and extracellular vesicles, which target various systemic organ systems to regulate metabolism, homeostasis, immune response. The global effects adipokines on metabolic events are well defined, but their impacts brain function pathology remain poorly defined. Receptors widely expressed brain. Mounting evidence has shown that leptin adiponectin cross blood–brain barrier, while for newly identified limited. Significantly, adipocyte secretion liable nutritional states, where defective circuitry, impaired neuroplasticity, elevated neuroinflammation symptomatic. Essentially, neurotrophic anti-inflammatory properties underlie neuroprotective roles neurodegenerative diseases. Besides, adipocyte-secreted lipids bloodstream act distant organs. In this article, we have reviewed five (leptin, adiponectin, chemerin, apelin, visfatin) two lipokines (palmitoleic acid lysophosphatidic acid) involving eating behavior, factors Understanding regulating these lead novel therapeutic strategies counteract associated disorders diseases, thus promote health.

Language: Английский

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Pathogenetic pathways of cognitive dysfunction and dementia in metabolic syndrome

Life Sciences, Journal Year: 2019, Volume and Issue: 237, P. 116932 - 116932

Published: Oct. 10, 2019

Language: Английский

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Exerkines and long-term synaptic potentiation: Mechanisms of exercise-induced neuroplasticity

Frontiers in Neuroendocrinology, Journal Year: 2022, Volume and Issue: 66, P. 100993 - 100993

Published: March 11, 2022

Physical exercise may improve cognitive function by modulating molecular and cellular mechanisms within the brain. We propose that facilitation of long-term synaptic potentiation (LTP)-related pathways, products induced physical (i.e., exerkines), is a crucial aspect exercise-effect on This review summarizes pathways are activated exerkines potentiate LTP. For total 16 exerkines, we indicated how blood brain exerkine levels altered depending type cardiovascular or resistance exercise) they respond to single bout acute multiple bouts chronic exercise). information be used for designing individualized programs. Finally, this serve direct future research towards fundamental gaps in our current knowledge regarding biophysical interactions between muscle activity at both system levels.

Language: Английский

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