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

Advanced Materials, Год журнала: 2024, Номер 36(18)

Опубликована: Янв. 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.

Язык: Английский

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

ACS Nano, Год журнала: 2024, Номер 18(11), С. 7890 - 7906

Опубликована: Март 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.

Язык: Английский

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Nano‐Brake Halts Mitochondrial Dysfunction Cascade to Alleviate Neuropathology and Rescue Alzheimer's Cognitive Deficits

Advanced Science, Год журнала: 2023, Номер 10(7)

Опубликована: Янв. 26, 2023

Abstract Mitochondrial dysfunction has been recognized as the key pathogenesis of most neurodegenerative diseases including Alzheimer's disease (AD). The dysregulation mitochondrial calcium ion (Ca 2+ ) homeostasis and permeability transition pore (mPTP), is a critical upstream signaling pathway that contributes to cascade in AD pathogenesis. Herein, “two‐hit braking” therapeutic strategy synergistically halt Ca overload mPTP opening put on brake proposed. To achieve this goal, magnesium (Mg ), natural antagonist, siRNA central regulator cyclophilin D (CypD), are co‐encapsulated into designed nano‐brake; A matrix metalloproteinase 9 (MMP9) activatable cell‐penetrating peptide (MAP) anchored surface nano‐brake overcome blood‐brain barrier (BBB) realize targeted delivery cells brain. Nano‐brake treatment efficiently halts cerebrovascular endothelial cells, neurons, microglia powerfully alleviates neuropathology rescues cognitive deficits. These findings collectively demonstrate potential advanced design nanotherapeutics pathways provide powerful for modifying therapy.

Язык: Английский

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Blood-brain barrier dysfunction and Alzheimer’s disease: associations, pathogenic mechanisms, and therapeutic potential

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Ноя. 13, 2023

Alzheimer’s disease (AD) is a common neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ), hyperphosphorylation tau, and neuroinflammation in brain. The blood–brain barrier (BBB) limits solutes from circulating blood entering brain, which essential for neuronal functioning. Focusing on BBB function important early detection AD in-depth study pathogenic mechanisms. However, mechanism alteration still unclear, hinders further research therapeutics that target to delay progression AD. exact timing vascular abnormalities complex cause-and-effect relationships remain uncertain. Thus, it necessary summarize emphasize this process. First, review, current evidence dysfunction summarized. Then, interrelationships mechanisms between risk factors AD, such as Aβ, neuroinflammation, apolipoprotein E (ApoE) genotype aging, were analyzed. Finally, we discuss status future directions therapeutic strategies targeting BBB. We hope these summaries or reviews will allow readers better understand relationship

Язык: Английский

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Identification of mitochondrial related signature associated with immune microenvironment in Alzheimer’s disease

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Июль 11, 2023

Abstract Background Alzheimer's disease (AD) is the most common neurodegenerative disease. Mitochondrial dysfunction and immune responses are important factors in pathogenesis of AD, but their crosstalk AD has not been studied. In this study, independent role interaction mitochondria-related genes cell infiltration were investigated using bioinformatics methods. Methods The datasets obtained from NCBI Gene Expression Omnibus (GEO), data mitochondrial was MitoCarta3.0 database. Subsequently, differential expression (DEGs) screening GSEA functional enrichment analysis performed. intersection DEGs related used to obtain MitoDEGs. MitoDEGs relevant determined by Least absolute shrinkage selection operator multiple support vector machine recursive feature elimination, as well protein–protein interactions (PPI) network random forest. 28 kinds cells analyzed ssGSEA, relationship between hub proportion levels verified models mice, OPA1 damage neuronal apoptosis investigated. Results functions pathways significantly enriched including response activation, IL1R pathway, metabolism, oxidative electron transport chain-oxphos system mitochondria. Hub closely based on PPI network, forest two learning algorithms. Five associated with neurological disorders identified biological function examination. found be correlated memory B cell, effector CD8 T activated dendritic natural killer type 17 helper Neutrophil, MDSC, plasmacytoid cell. These can also predict risk have good diagnostic efficacy. addition, mRNA BDH1, TRAP1, OPA1, DLD mice consistent results analysis, SPG7 showed a downward trend. Meanwhile, overexpression alleviated induced Aβ1-42. Conclusions potential identified. Their microenvironment may play crucial occurrence prognosis which provides new insight for studying exploring targets.

Язык: Английский

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Oxygen metabolism abnormality and Alzheimer's disease: An update

Redox Biology, Год журнала: 2023, Номер 68, С. 102955 - 102955

Опубликована: Ноя. 8, 2023

Oxygen metabolism abnormality plays a crucial role in the pathogenesis of Alzheimer's disease (AD) via several mechanisms, including hypoxia, oxidative stress, and mitochondrial dysfunction. Hypoxia condition usually results from living high-altitude habitat, cardiovascular cerebrovascular diseases, chronic obstructive sleep apnea. Chronic hypoxia has been identified as significant risk factor for AD, showing an aggravation various pathological components such amyloid β-protein (Aβ) metabolism, tau phosphorylation, dysfunction, neuroinflammation. It is known that excessive hyperoxia can both result stress Oxidative dysfunction increase Aβ proteins lead to redox imbalance, thus forming vicious cycle exacerbating AD pathology. Hyperbaric oxygen therapy (HBOT) non-invasive intervention its capacity significantly enhance cerebral oxygenation levels, which attenuate aggregation, However, further investigation imperative determine optimal pressure, duration exposure, frequency HBOT sessions. In this review, we explore prospects with aim enhancing our understanding underlying molecular mechanisms AD. Current research aimed at attenuating abnormalities holds promise providing novel therapeutic approaches

Язык: Английский

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Ferroptosis in ulcerative colitis: Potential mechanisms and promising therapeutic targets

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 175, С. 116722 - 116722

Опубликована: Май 9, 2024

Ulcerative colitis (UC) is a complex immune-mediated chronic inflammatory bowel disease. It mainly characterized by diffuse inflammation of the colonic and rectal mucosa with barrier function impairment. Identifying new biomarkers for development more effective UC therapies remains pressing task current research. Ferroptosis newly identified form regulated cell death iron-dependent lipid peroxidation. As research deepens, ferroptosis has been demonstrated to be involved in pathological processes numerous diseases. A growing body evidence suggests that pathogenesis associated ferroptosis, regulation provides opportunities treatment. However, specific mechanisms which participates remain fully thoroughly investigated. Therefore, this review, we focus on advances mechanism recent years describe potential role UC. In addition, explore underlying crosslinked pathway between other such as macrophages, neutrophils, autophagy, endoplasmic reticulum stress, gut microbiota Finally, also summarize compounds may act inhibitors future.

Язык: Английский

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Interactions between nanoparticles and pathological changes of vascular in Alzheimer’s disease

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 207, С. 115219 - 115219

Опубликована: Фев. 23, 2024

Язык: Английский

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Matrix Metalloproteinase-Responsive Drug Delivery Systems

Bioconjugate Chemistry, Год журнала: 2023, Номер 34(8), С. 1349 - 1365

Опубликована: Авг. 3, 2023

Matrix metalloproteinases (MMPs) are a class of endopeptidases that dependent on zinc and facilitate the degradation extracellular matrix (ECM) proteins, thereby playing pivotal parts in human physiology pathology. MMPs regulate normal tissue cellular functions, including development, remodeling, angiogenesis, bone formation, wound healing. Several diseases, cancer, inflammation, cardiovascular nervous system disorders, have been linked to dysregulated expression specific MMP subtypes, which can promote tumor progression, metastasis, inflammation. Various MMP-responsive drug delivery release systems developed by harnessing cleavage activities overexpression affected regions. Herein, we review structure, substrates, physiological pathological functions various highlight strategies for designing nanoparticles improve targeting efficiency, penetration, protection therapeutic payloads.

Язык: Английский

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Nanomedicines for Alzheimer's disease: Therapies based on pathological mechanisms

Brain‐X, Год журнала: 2023, Номер 1(3)

Опубликована: Июль 28, 2023

Abstract Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Because of complex pathogenesis AD and unique location lesions, effective clinical treatment strategies for this remain elusive. However, development nanotechnology has allowed a new era to emerge. nanomedicines are products interdisciplinary research that enable high precision targeted delivery. Additionally, they can specifically regulate various pathogenic factors. This review focuses on based pathological mechanisms target lesions. We also discuss precise regulatory effects (including nanomaterials themselves) proteins, neuroinflammatory molecules, other summarize trials have examined drugs, highlighting progress in their translation. Nanotechnology‐based nascent field, complete cure distant at present; therefore, we elaborate shortcomings current nanomedicines. Finally, prospects guide future

Язык: Английский

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