APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer’s disease pathology and brain diseases

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: Sept. 24, 2022

Abstract ApoE is the major lipid and cholesterol carrier in CNS. There are three human polymorphisms, apoE2, apoE3, apoE4, genetic expression of APOE4 one most influential risk factors for development late-onset Alzheimer's disease (AD). Neuroinflammation has become third hallmark AD, together with Amyloid-β plaques neurofibrillary tangles hyperphosphorylated aggregated tau protein. This review aims to broadly extensively describe differential aspects concerning apoE. Starting from evolution apoE how APOE's single-nucleotide polymorphisms affect its structure, function, involvement during health disease. reflects on impact critical AD pathology, such as neuroinflammatory response, particularly effect APOE astrocytic microglial function dynamics, synaptic amyloid-β load, autophagy, cell–cell communication. We discuss affecting pathology combined genotype, sex, age, diet, physical exercise, current therapies clinical trials field. The genotype other neurodegenerative diseases characterized by overt inflammation, e.g., alpha- synucleinopathies Parkinson's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis, multiple also addressed. Therefore, this gathers relevant findings related up date implications CNS pathologies provide a deeper understanding knowledge

Language: Английский

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Mitochondria: It is all about energy

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

Published: April 25, 2023

Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron calcium homeostasis the of hormones neurotransmitters, such as melatonin. They enable influence communication at all physical levels through interaction with other organelles, nucleus, outside environment. The literature suggests crosstalk between mitochondria circadian clocks, gut microbiota, immune system. might even be hub supporting integrating activity across these domains. Hence, they (missing) link Mitochondrial dysfunction related metabolic syndrome, neuronal diseases, cancer, cardiovascular infectious inflammatory disorders. In this regard, diseases Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), pain are discussed. This review focuses on understanding mitochondrial action that allow for maintenance pathways toward dysregulated mechanisms. Although have allowed us adapt changes over course evolution, turn, evolution has shaped mitochondria. Each evolution-based intervention influences its own way. use physiological stress triggers tolerance stressor, achieving adaptability resistance. describes strategies could recover functioning providing comprehensive, root-cause-focused, integrative approach recovering treating people suffering diseases.

Language: Английский

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Aging of mesenchymal stem cell: machinery, markers, and strategies of fighting

Cellular & Molecular Biology Letters, Journal Year: 2022, Volume and Issue: 27(1)

Published: Aug. 19, 2022

Human mesenchymal stem cells (MSCs) are primary multipotent capable of differentiating into osteocytes, chondrocytes, and adipocytes when stimulated under appropriate conditions. The role MSCs in tissue homeostasis, aging-related diseases, cellular therapy is clinically suggested. As aging a universal problem that has large socioeconomic effects, an improved understanding the concepts can direct public policies reduce its adverse impacts on healthcare system humanity. Several studies have been carried out over several years to understand phenomenon different factors affecting human aging. A reduced ability adult cell populations reproduce regenerate one main contributors process. In this context, senescence major challenge front advancement. Many factors, ranging from genetic metabolic pathways extrinsic through various signaling pathways, involved regulating mechanism MSC senescence. To better reverse senescence, review highlights underlying mechanisms signs discusses strategies combat

Language: Английский

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Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 11, 2024

Abstract Diet, serving as a vital source of nutrients, exerts profound influence on human health and disease progression. Recently, dietary interventions have emerged promising adjunctive treatment strategies not only for cancer but also neurodegenerative diseases, autoimmune cardiovascular metabolic disorders. These demonstrated substantial potential in modulating metabolism, trajectory, therapeutic responses. Metabolic reprogramming is hallmark malignant progression, deeper understanding this phenomenon tumors its effects immune regulation significant challenge that impedes eradication. Dietary intake, key environmental factor, can tumor metabolism. Emerging evidence indicates might affect the nutrient availability tumors, thereby increasing efficacy treatments. However, intricate interplay between pathogenesis other diseases complex. Despite encouraging results, mechanisms underlying diet-based remain largely unexplored, often resulting underutilization management. In review, we aim to illuminate various interventions, including calorie restriction, fasting-mimicking diet, ketogenic protein restriction high-salt high-fat high-fiber aforementioned diseases. We explore multifaceted impacts these encompassing their immunomodulatory effects, biological impacts, molecular mechanisms. This review offers valuable insights into application therapies

Language: Английский

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Antioxidant Compounds from Edible Mushrooms as Potential Candidates for Treating Age-Related Neurodegenerative Diseases

Nutrients, Journal Year: 2023, Volume and Issue: 15(8), P. 1913 - 1913

Published: April 15, 2023

The last century has seen an increase in our life expectancy. As a result, various age-related diseases, such as neurodegenerative diseases (NDs), have emerged, representing new challenges to society. Oxidative stress (OS), condition of redox imbalance resulting from excessive production reactive oxygen species, represents common feature that characterizes the brains elderly people, thus contributing NDs. Consequently, antioxidant supplementation or dietary intake antioxidant-containing foods could represent effective preventive and therapeutic intervention maintain integrity survival neurons counteract pathologies associated with aging. Food contains numerous bioactive molecules beneficial actions for human health. To this purpose, wide range edible mushrooms been reported produce different compounds phenolics, flavonoids, polysaccharides, vitamins, carotenoids, ergothioneine, others, which might be used enhance defenses and, consequently, prevention neurological diseases. In review, we summarized role oxidative NDs, focusing on current knowledge present mushrooms, highlighting their potential preserve healthy aging by counteracting age-associated

Language: Английский

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Mitochondrial dysfunction and its association with age-related disorders

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: July 2, 2024

Aging is a complex process that features functional decline in many organelles. Various factors influence the aging process, such as chromosomal abnormalities, epigenetic changes, telomere shortening, oxidative stress, and mitochondrial dysfunction. Mitochondrial dysfunction significantly impacts because mitochondria regulate cellular energy, balance, calcium levels. integrity maintained by mitophagy, which helps maintain homeostasis, prevents ROS production, protects against mtDNA damage. However, increased uptake stress can disrupt membrane potential permeability, leading to apoptotic cascade. This disruption causes production of free radicals, modification accumulation DNA mutations, contribute aging. dysfunction, resulting from structural linked age-related degenerative diseases. review focuses on its implications disorders, anti-aging strategies through targeting

Language: Английский

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Longevity and anti-aging effects of curcumin supplementation

GeroScience, Journal Year: 2024, Volume and Issue: 46(3), P. 2933 - 2950

Published: Feb. 27, 2024

Language: Английский

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Antioxidant Systems as Modulators of Ferroptosis: Focus on Transcription Factors

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 298 - 298

Published: Feb. 28, 2024

Ferroptosis is a type of programmed cell death that differs from apoptosis, autophagy, and necrosis related to several physio-pathological processes, including tumorigenesis, neurodegeneration, senescence, blood diseases, kidney disorders, ischemia–reperfusion injuries. linked iron accumulation, eliciting dysfunction antioxidant systems, which favor the production lipid peroxides, membrane damage, ultimately, death. Thus, signaling pathways evoking ferroptosis are strongly associated with those protecting cells against excess and/or lipid-derived ROS. Here, we discuss interaction between metabolic particular focus on transcription factors implicated in regulation ferroptosis, either as triggers peroxidation or defense pathways.

Language: Английский

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The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 6, 2024

Abstract Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. -derived functional molecules are not well understood. Microbiome-secreted proteins act as key arbitrators host-microbiome crosstalk through interactions with host cells the important for understanding relationships. Herein, we report biological function Amuc_1409, a previously uncharacterised muciniphila- secreted protein. Amuc_1409 increased stem cell (ISC) proliferation regeneration ex vivo organoids models radiation- or chemotherapeutic drug-induced injury natural aging male mice. Mechanistically, promoted E-cadherin/β-catenin complex dissociation via interaction E-cadherin, resulting activation Wnt/β-catenin signaling. Our results demonstrate that plays crucial role homeostasis ISC activity an E-cadherin-dependent manner is promising biomolecule maintaining health.

Language: Английский

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The beneficial effects of curcumin on aging and age-related diseases: from oxidative stress to antioxidant mechanisms, brain health and apoptosis

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 20, 2025

Aging and age-related disease are among the most common challenging issues worldwide. During aging process, accumulation of oxidative stress, DNA damage, telomere dysfunction, other related changes lead to cellular dysfunction development diseases such as neurodegenerative cardiovascular conditions. Curcumin is a widely-used dietary supplement against various cancer, diabetes, aging. This agent mediates its effects through several mechanisms, including reduction reactive oxygen species (ROS) stress-induced well modulation subcellular signaling pathways AMPK, AKT/mTOR, NF-κB. These involved in senescence inflammation, their can improve cell function help prevent disease. In induce apoptosis variety different tumor lines. also activates redox reactions within cells inducing ROS production that leads upregulation receptors on membrane. upregulate expression activity p53 inhibits proliferation increases apoptosis. Furthermore, curcumin has potent inhibitory effect nuclear factor kappa B (NF-κB) cyclooxygenase-2 (COX-2) , which overexpression antiapoptosis genes Bcl-2 . It attenuate regulation phosphoinositide 3-kinases ( PI3K ) increase mitogen-activated protein kinases (MAPKs) endogenous ROS. Therefore, herein, we aim summarize how affect epigenetic processes (such stress) order change aging-related mechanisms. discuss roles diseases, Alzheimer, Parkinson, osteoporosis, diseases.

Language: Английский

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