Engineered mesenchymal stem cell-derived extracellular vesicles: A state-of-the-art multifunctional weapon against Alzheimer's disease

Theranostics, Journal Year: 2023, Volume and Issue: 13(4), P. 1264 - 1285

Published: Jan. 1, 2023

With the increase of population aging, number Alzheimer's disease (AD) patients is also increasing.According to current estimates, approximately 11% people over 65 suffer from AD, and that percentage rises 42% among 85.However, no effective treatment capable decelerating or stopping AD progression available.Furthermore, AD-targeted drugs composed synthetic molecules pose concerns regarding biodegradation, clearance, immune response, neurotoxicity.Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are essential intercellular communication mediators holding great promise as therapeutics owing their biocompatibility, versatility, effortless storage, superior safety, ability transport messenger noncoding RNAs, proteins, lipids, DNAs, other bioactive compounds derived cells.The functionalisation engineering strategies MSC-EVs highlighted (e.g.preconditioning, drug loading, surface modification, artificial EV fabrication), which could improve by multiple therapeutic effects, including clearing abnormal protein accumulation achieving neuroprotection immunomodulatory effects.Herein, this review summarises state-of-the-art engineer MSC-EVs, discusses progress in use therapeutics, presents perspectives challenges associated with related clinical applications, concludes engineered show immense potential therapy.

Language: Английский

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Leveraging electronic health records and knowledge networks for Alzheimer’s disease prediction and sex-specific biological insights

Nature Aging, Journal Year: 2024, Volume and Issue: 4(3), P. 379 - 395

Published: Feb. 21, 2024

Identification of Alzheimer's disease (AD) onset risk can facilitate interventions before irreversible progression. We demonstrate that electronic health records from the University California, San Francisco, followed by knowledge networks (for example, SPOKE) allow for (1) prediction AD and (2) prioritization biological hypotheses, (3) contextualization sex dimorphism. trained random forest models predicted on a cohort 749 individuals with 250,545 controls mean area under receiver operating characteristic 0.72 (7 years prior) to 0.81 (1 day prior). further harnessed matched identify conditions predictive power onset. Knowledge highlight shared genes between multiple top predictors APOE, ACTB, IL6 INS). Genetic colocalization analysis supports association hyperlipidemia at APOE locus, as well stronger female osteoporosis locus near MS4A6A. therefore show how clinical data be utilized early identification personalized hypotheses.

Language: Английский

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Intracellular Molecular Targets and Signaling Pathways Involved in Antioxidative and Neuroprotective Effects of Cannabinoids in Neurodegenerative Conditions

Antioxidants, Journal Year: 2022, Volume and Issue: 11(10), P. 2049 - 2049

Published: Oct. 18, 2022

In the last few decades, endocannabinoids, plant-derived cannabinoids and synthetic have received growing interest as treatment options in neurodegenerative conditions. various experimental settings, they displayed antioxidative, anti-inflammatory, antiapoptotic, immunomodulatory, neuroprotective effects. However, due to numerous targets downstream effectors of their action, cellular molecular mechanisms underlying these effects are rather complex still under discussion. Cannabinoids able neutralize free radicals modulate production reactive oxygen species activity antioxidative systems acting on CB1 CB2 cannabinoid receptors. The activation receptors stimulates signaling pathways involved defense survival (such phosphoinositide 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK), Nrf2 pathways) regulates glutamatergic signaling, N-methyl-D-aspartate (NMDA) receptors, calcium influx, induction Ca2+-regulated cascades, whereas mediated by suppression microglial release prooxidative proinflammatory mediators. This review summarizes main new advances understanding cannabinoids. Because plethora possible pharmacological interventions related oxidative stress cannabinoid-mediated neuroprotection, future research should be directed towards a better interplay between activated signal transduction with aim improve efficacy targeting endocannabinoid system.

Language: Английский

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Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 20(1), P. 709 - 727

Published: Oct. 9, 2023

Abstract Aging, tau pathology, and chronic inflammation in the brain play crucial roles synaptic loss, neurodegeneration, cognitive decline tauopathies, including Alzheimer's disease. Senescent cells accumulate aging brain, accelerate process, promote tauopathy progression through their abnormal inflammatory secretome known as senescence‐associated secretory phenotype (SASP). Tau oligomers (TauO)—the most neurotoxic species—are to induce senescence SASP, which subsequently neuropathology, inflammation, oxidative stress, dysfunction, neuronal death, dysfunction. TauO, are associated with heterogeneity decline. However, underlying mechanisms driving disease remain largely unknown, impeding development of therapies for tauopathies. Based on clinical preclinical evidence, this review highlights critical role TauO neurodegeneration. We discuss key knowledge gaps potential strategies targeting treat Highlights Senescence, oligomeric (TauO), process contributing highlight target tauopathies while addressing gaps.

Language: Английский

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

Journal of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: 96(4), P. 1353 - 1382

Published: Nov. 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.

Language: Английский

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High-Fat Diets in Animal Models of Alzheimer’s Disease: How Can Eating Too Much Fat Increase Alzheimer’s Disease Risk?

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 97(3), P. 977 - 1005

Published: Jan. 9, 2024

High dietary intake of saturated fatty acids is a suspected risk factor for neurodegenerative diseases, including Alzheimer’s disease (AD). To decipher the causal link behind these associations, high-fat diets (HFD) have been repeatedly investigated in animal models. Preclinical studies allow full control over composition, avoiding ethical concerns clinical trials. The goal present article to provide narrative review reports on HFD models AD. Eligibility criteria included mouse AD fed defined as > 35% fat/weight and western containing 1% cholesterol or 15% sugar. MEDLINE Embase databases were searched from 1946 August 2022, 32 preclinical review. HFD-induced obesity metabolic disturbances such insulin resistance glucose intolerance replicated most studies, but with methodological variability. Most found an aggravating effect brain Aβ pathology, whereas tau pathology has much less studied, results are more equivocal. While show impairment cognitive behavior, confounding factors may blur their interpretation. In summary, despite conflicting results, exposing rodents highly enriched fat induces not only defects, also often accompanied by aggravated neuropathological markers, notably burden. Although there important variations between methods, particularly lack diet characterization, collectively suggest that excessive should be avoided order lower incidence

Language: Английский

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The Dual Role of Amyloid Beta-Peptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer’s Disease Etiopathology

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1208 - 1208

Published: Oct. 8, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and it currently the seventh leading cause of death worldwide. It characterized by extracellular aggregation amyloid β-peptide (Aβ) into oligomers fibrils that synaptotoxicity neuronal death. Aβ exhibits dual role in promoting oxidative stress inflammation. This review aims to unravel intricate connection between these processes their contribution AD progression. The delves AD, focusing on involvement metals, mitochondrial dysfunction, biomolecule oxidation. distinct yet overlapping concept nitro-oxidative also discussed, detailing roles nitric oxide, perturbations, cumulative impact production neurotoxicity. Inflammation examined through astroglia microglia function, elucidating response within brain. blood-brain barrier oligodendrocytes are considered context pathophysiology. We current diagnostic methodologies emerging therapeutic strategies aimed at mitigating inflammation, thereby offering potential treatments for halting or slowing comprehensive synthesis underscores pivotal bridging advancing our understanding informing future research treatment paradigms.

Language: Английский

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Mind the Gap: Unraveling the Intricate Dance Between Alzheimer’s Disease and Related Dementias and Bone Health

Current Osteoporosis Reports, Journal Year: 2024, Volume and Issue: 22(1), P. 165 - 176

Published: Jan. 29, 2024

Abstract Purpose of Review This review examines the linked pathophysiology Alzheimer’s disease/related dementia (AD/ADRD) and bone disorders like osteoporosis. The emphasis is on “inflammaging”—a low-level inflammation common to both, its implications in an aging population. Recent Findings Aging intensifies both ADRD deterioration. Notably, patients have a heightened fracture risk, impacting morbidity mortality, though it uncertain if fractures worsen ADRD. Therapeutically, agents targeting pathways, especially Nuclear factor kappa-light-chain-enhancer activated B cells (NF-kB) TNF-α, appear beneficial for conditions. Additionally, treatments Sirtuin 1 (SIRT-1), known anti-inflammatory neuroprotective properties, are gaining attention. Summary interconnectedness AD/ADRD health necessitates unified treatment approach. By addressing shared mechanisms, we can potentially transform therapeutic strategies, enriching our understanding refining care society. article part series multiple manuscripts designed determine utility using artificial intelligence writing scientific reviews.

Language: Английский

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Gut microbial metabolism in Alzheimer's disease and related dementias

Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(6), P. e00470 - e00470

Published: Oct. 1, 2024

Multiple studies over the last decade have established that Alzheimer's disease and related dementias (ADRD) are associated with changes in gut microbiome. These alterations organismal composition result abundances of functions encoded by microbial community, including metabolic capabilities, which likely impact host mechanisms. Gut microbes access dietary components other molecules made produce metabolites can enter circulation cross blood-brain barrier (BBB). In recent years, several been or shown to influence pathways relevant ADRD pathology. include short chain fatty acids, secondary bile tryptophan derivatives (such as kynurenine, serotonin, tryptamine, indoles), trimethylamine/trimethylamine N-oxide. Notably, some these BBB various effects on brain, modulating release neurotransmitters neuronal function, inducing oxidative stress inflammation, impacting synaptic function. Microbial also central nervous system through immune, enteroendocrine, enteric pathways, perturbations turn function peripheral immune responses, well integrity, homeostasis neurogenesis, glial cell maturation activation. This review examines evidence supporting notion is influenced microbiota its metabolites. The potential therapeutic advantages for preventing treating discussed, highlighting their role developing new treatments.

Language: Английский

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Translational Research on Bee Pollen as a Source of Nutrients: A Scoping Review from Bench to Real World

Nutrients, Journal Year: 2023, Volume and Issue: 15(10), P. 2413 - 2413

Published: May 22, 2023

The emphasis on healthy nutrition is gaining a forefront place in current biomedical sciences. Nutritional deficiencies and imbalances have been widely demonstrated to be involved the genesis development of many world-scale public health burdens, such as metabolic cardiovascular diseases. In recent years, bee pollen emerging scientifically validated candidate, which can help diminish conditions through nutritional interventions. This matrix being extensively studied, has proven very rich well-balanced nutrient pool. this work, we reviewed available evidence interest source. We mainly focused richness nutrients its possible roles main pathophysiological processes that are directly linked imbalances. scoping review analyzed scientific works published last four focusing clearest inferences perspectives translate cumulated experimental preclinical into clinically relevant insights. promising uses for malnutrition, digestive health, disorders, other bioactivities could helpful readjust homeostasis (as it also true case anti-inflammatory or anti-oxidant needs), well benefits diseases, were identified. knowledge gaps identified, along with practical challenges hinder establishment fructification these uses. A complete data collection made major range botanical species allows more robust clinical information.

Language: Английский

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