Exosomes: potential targets for the diagnosis and treatment of neuropsychiatric disorders DOI Creative Commons

Haorao Li,

Yanling Yuan,

Qinglian Xie

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 29, 2024

Abstract The field of neuropsychiatry is considered a middle ground between neurological and psychiatric disorders, thereby bridging the conventional boundaries matter mind, consciousness, function. Neuropsychiatry aims to evaluate treat cognitive, behavioral, emotional disorders in individuals with conditions. However, pathophysiology these not yet fully understood, objective biological indicators for conditions are currently lacking. Treatment options also limited due blood–brain barrier, which results poor treatment effects. Additionally, many drugs, particularly antipsychotic have adverse reactions, make them difficult tolerate patients. As result, patients often abandon owing reactions. Since discovery exosomes 1983, they been extensively studied various diseases their potential as nanocellulators information exchange cells. Because can freely travel center periphery, brain-derived reflect state brain, has considerable advantages diagnosis treatment. In addition, administration engineered improve therapeutic efficacy, allow lesion targeting, ensure drug stability, prevent systemic Therefore, this article reviews source function exosomes, relationship pathological mechanism neuropsychiatric application disorders.

Language: Английский

The blood–brain barrier: Structure, regulation and drug delivery DOI Creative Commons
Di Wu, Qi Chen, Xiaojie Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 25, 2023

Abstract Blood–brain barrier (BBB) is a natural protective membrane that prevents central nervous system (CNS) from toxins and pathogens in blood. However, the presence of BBB complicates pharmacotherapy for CNS disorders as most chemical drugs biopharmaceuticals have been impeded to enter brain. Insufficient drug delivery into brain leads low therapeutic efficacy well aggravated side effects due accumulation other organs tissues. Recent breakthrough materials science nanotechnology provides library advanced with customized structure property serving powerful toolkit targeted delivery. In-depth research field anatomical pathological study on further facilitates development brain-targeted strategies enhanced crossing. In this review, physiological different cells contributing are summarized. Various emerging permeability regulation crossing including passive transcytosis, intranasal administration, ligands conjugation, coating, stimuli-triggered disruption, overcome obstacle highlighted. Versatile systems ranging organic, inorganic, biologics-derived their synthesis procedures unique physio-chemical properties summarized analyzed. This review aims provide an up-to-date comprehensive guideline researchers diverse fields, offering perspectives system.

Language: Английский

Citations

598
New strategies of neurodegenerative disease treatment with extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) DOI Creative Commons
Chella Perumal Palanisamy, Jinjin Pei, Phaniendra Alugoju

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 13(12), P. 4138 - 4165

Published: Jan. 1, 2023

Neurodegenerative diseases are characterized by the progressive loss of neurons and intricate interactions between different cell types within affected regions.Reliable biomarkers that can accurately reflect disease activity, diagnose, monitor progression neurodegenerative crucial for development effective therapies.However, identifying suitable has been challenging due to heterogeneous nature these diseases, affecting specific subsets in brain regions.One promising approach promoting regeneration recovery involves transplantation mesenchymal stem cells (MSCs).MSCs have demonstrated ability modulate immune system, promote neurite outgrowth, stimulate angiogenesis, repair damaged tissues, partially through release their extracellular vesicles (EVs).MSC-derived EVs retain some therapeutic characteristics parent MSCs, including regulate facilitate tissue repair.This review aims explore potential MSC-derived as an emerging strategy highlighting role modulating neuronal recovery.By elucidating mechanisms which exert effects, we advance our understanding leverage novel treatment approaches field diseases.

Language: Английский

Citations

66
Oral feeding of nanoplastics affects brain function of mice by inducing macrophage IL-1 signal in the intestine DOI Creative Commons
Qianyu Yang,

Huaxing Dai,

Ying Cheng

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(4), P. 112346 - 112346

Published: April 1, 2023

Nanoplastics (NPs) as contaminants in food and water have drawn increasing public attention. However, little is known about how NPs shape the gut immune landscape after injection. In this study, we fabricate (∼500 nm) microplastics (MPs) (∼2 μm) evaluate their vivo effects by feeding them to mice. The results suggest that show a better ability induce macrophage activation than MPs. addition, trigger interleukin-1 (IL-1)-producing reprogramming via inducing lysosomal damage. More importantly, IL-1 signaling from intestine can affect brain immunity, leading microglial Th17 differentiation, all of which correlates with decline cognitive short-term memory NP-fed Thus, study provides insight into mechanism action gut-brain axis, delineates way reduce function, highlights importance fixing plastic pollution problem worldwide.

Language: Английский

Citations

58
Engineered mesenchymal stem cell-derived extracellular vesicles: A state-of-the-art multifunctional weapon against Alzheimer's disease DOI Creative Commons
Tong Yin, Yan Liu, Wenbo Ji

et al.

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

Citations

47
Customized Intranasal Hydrogel Delivering Methylene Blue Ameliorates Cognitive Dysfunction against Alzheimer's Disease DOI
Yujing Liu, Yun Tan,

Guopan Cheng

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(19)

Published: Feb. 23, 2024

Abstract The accumulation of hyperphosphorylated tau protein aggregates is a key pathogenic event in Alzheimer's disease (AD) and induces mitochondrial dysfunction reactive oxygen species overproduction. However, the treatment AD remains challenging owning to hindrance caused by blood–brain barrier (BBB) complex pathology AD. Nasal delivery represents an effective means circumventing BBB delivering drugs brain. In this study, black phosphorus (BP) used as drug carrier, well antioxidant, loaded with aggregation inhibitor, methylene blue (MB), obtain BP‐MB. For intranasal (IN) delivery, thermosensitive hydrogel fabricated cross‐linking carboxymethyl chitosan aldehyde Pluronic F127 (F127‐CHO) micelles. BP‐MB nanocomposite incorporated into BP‐MB@Gel. BP‐MB@Gel could be injected intranasally, providing high nasal mucosal retention controlled release. After IN administration, continuously released delivered brain, exerting synergistic therapeutic effects suppressing neuropathology, restoring function, alleviating neuroinflammation, thus inducing cognitive improvements mouse models These findings highlight potential strategy for brain‐targeted management pathologies

Language: Английский

Citations

34
Revitalizing Ancient Mitochondria with Nano‐Strategies: Mitochondria‐Remedying Nanodrugs Concentrate on Disease Control DOI

Xingyu Long,

Min Liu,

Yayun Nan

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(18)

Published: Jan. 15, 2024

Abstract Mitochondria, widely known as the energy factories of eukaryotic cells, have a myriad vital functions across diverse cellular processes. Dysfunctions within mitochondria serve catalysts for various diseases, prompting widespread demise. Mounting research on remedying damaged indicates that constitute valuable target therapeutic intervention against diseases. But less clinical practice and lower recovery rate imply limitation traditional drugs, which need further breakthrough. Nanotechnology has approached favorable regiospecific biodistribution high efficacy by capitalizing excellent nanomaterials targeting drug delivery. Mitochondria‐remedying nanodrugs achieved ideal effects. This review elucidates significance in cells organs, while also compiling mortality data related Correspondingly, nanodrug‐mediate strategies applicable mitochondria‐remedying disease are detailed, with full understanding roles dysfunction advantages nanodrugs. In addition, future challenges directions discussed. conclusion, this provides comprehensive insights into design development nanodrugs, aiming to help scientists who desire extend their fields engage interdisciplinary subject.

Language: Английский

Citations

29
In Situ Self-Assembled Phytopolyphenol-Coordinated Intelligent Nanotherapeutics for Multipronged Management of Ferroptosis-Driven Alzheimer’s Disease DOI

Yining Liu,

Dongju Zhao, Fan Yang

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(11), P. 7890 - 7906

Published: March 6, 2024

Ferroptosis is a vital driver of pathophysiological consequences Alzheimer's disease (AD). High-efficiency pharmacological inhibition ferroptosis requires comprehensive coordination diverse abnormal intracellular events, which an urgent problem and great challenge for its application in AD treatment. Herein, triphenylphosphonium-modified quercetin-derived smart nanomedicine (TQCN) developed multipronged anti-ferroptosis therapy AD. Taking advantage the favorable brain-targeting mitochondria-locating properties, TQCN can efficiently chelate iron through phytopolyphenol-mediated spontaneous self-assemble into metal-phenolic nanocomplexes situ, exerting escalating exogenous offensive effects to attenuate overload induced free radical burst. Meanwhile, Nrf2 signaling-mediated endogenous defensive system reconstituted restore metabolism homeostasis represented by export storage enhance cytoprotective antioxidant cascades lipid peroxidation detoxification. Benefiting from multifaceted regulation pathogenic processes triggering ferroptosis, treatment ameliorate various neurodegenerative manifestations associated with brain deposition rescue severe cognitive decline mice. This work displays promise situ self-assembled phytopolyphenol-coordinated intelligent nanotherapeutics as advanced candidates against ferroptosis-driven progression.

Language: Английский

Citations

20
Amyloid Precursor Protein and Alzheimer’s Disease DOI Open Access

Kseniia S. Orobets,

Andrey L. Karamyshev

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14794 - 14794

Published: Sept. 30, 2023

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders associated with age or inherited mutations. It characterized by severe dementia in late stages that affect memory, cognitive functions, and daily life overall. AD progression linked to accumulation cytotoxic amyloid beta (Aβ) hyperphosphorylated tau protein combined other pathological features such as synaptic loss, defective energy metabolism, imbalances protein, metal homeostasis. Several treatment options for are under investigation, including antibody-based therapy stem cell transplantation. Amyloid precursor (APP) a membrane considered play main role pathology. known APP physiological conditions follows non-amyloidogenic pathway; however, it can proceed an amyloidogenic scenario, which leads generation extracellular deleterious Aβ plaques. Not all steps biogenesis clear so far, these questions should be addressed future studies. complex chronic many factors contribute progression.

Language: Английский

Citations

34
Exosome-laden injectable self-healing hydrogel based on quaternized chitosan and oxidized starch attenuates disc degeneration by suppressing nucleus pulposus senescence DOI Creative Commons
Ming Guan, Can Liu, Qiangqiang Zheng

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 232, P. 123479 - 123479

Published: Jan. 30, 2023

Disc degeneration is the common pathology underlying various degenerative spinal disorders and currently there no effective cure. Here, we found nucleus pulposus (NP) cell senescence was closely associated with severity of disc degeneration, exosomes (Exos) derived from mesenchymal stem cells (MSCs) ameliorated NP promoted extracellular matrix (ECM) deposition. As chitosan-based hydrogels have been widely used as vehicles to deliver Exos due their prominent antibacterial capacity, biocompatibility, biodegradability, developed an Exos-laden hydrogel based on quaternized chitosan (QCS) oxidized starch (OST) treat degeneration. The synthesized QCS-OST injectable, self-healing, biocompatible, demonstrated desirable pore size, injectable properties, sustainable release Exos. In a rat model QCS-OST/Exos able rejuvenate senescence, promote ECM remodeling, partially restore structures annulus fibrosis. Our findings suggested that novel therapeutic strategy for treating via alleviating senescence.

Language: Английский

Citations

32
Multifunctional structural color triboelectric microneedle patches for psoriasis treatment DOI Creative Commons
Yu Wang, Xiaoxuan Zhang, Guopu Chen

et al.

Matter, Journal Year: 2023, Volume and Issue: 6(5), P. 1555 - 1568

Published: March 29, 2023

Language: Английский

Citations

27