Alzheimer’s Disease: Treatment Strategies and Their Limitations

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 13954 - 13954

Published: Nov. 12, 2022

Alzheimer’s disease (AD) is the most frequent case of neurodegenerative and becoming a major public health problem all over world. Many therapeutic strategies have been explored for several decades; however, there still no curative treatment, priority remains prevention. In this review, we present an update on clinical physiological phase AD spectrum, modifiable non-modifiable risk factors treatment with focus prevention strategies, then research models used in AD, followed by discussion limitations. The methods can significantly slow evolution are currently best strategy possible before advanced stages disease. Indeed, current drug treatments only symptomatic effects, disease-modifying not yet available. Drug delivery to central nervous system complex process represents challenge developing preventive strategies. Studies underway test new techniques facilitate bioavailability molecules brain. After deep study literature, find use soft nanoparticles, particular nanoliposomes exosomes, as innovative approach reducing solving problems brain bioavailability. show promising role exosomes smart systems able penetrate blood–brain barrier target tissues. Finally, different administration neurological disorders discussed. One intranasal which should be preclinical studies diseases.

Language: Английский

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

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

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Drug delivery strategies with lipid-based nanoparticles for Alzheimer’s disease treatment

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 10, 2025

Alzheimer's disease (AD) is a distinctive form of dementia characterized by age-related cognitive decline and memory impairment. A key hallmark AD the irreversible overaccumulation beta-amyloid (Aβ) in brain, associated with neuroinflammation neuronal death. Although Aβ clearance immunoregulation have been major therapeutic strategies for AD, highly selective transport across blood–brain barrier (BBB) negatively affects delivery efficacy drugs without ability to cross BBB. In this review, we discuss potential lipid-based nanoparticles (LBNs) as promising vehicles drug treatment. LBNs, composed phospholipid mono- or bilayer, attracted attention due their exceptional cellular penetration capabilities loading capabilities, which also facilitate cargo transcytosis Recent advances development engineering LBNs overcome existing limitations current clinical approaches treatment addressing off-target effects low efficacy. Here, review pathways BBB, well various types therapy, including exosomes, liposomes, solid lipid (SLNs), nanostructured carriers (NLCs), elucidate properties, preparation methodologies, efficacy, thereby offering innovative avenues novel translation therapy.

Language: Английский

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Brain‐Penetration and Neuron‐Targeting DNA Nanoflowers Co‐Delivering miR‐124 and Rutin for Synergistic Therapy of Alzheimer's Disease

Small, Journal Year: 2022, Volume and Issue: 18(14)

Published: Feb. 19, 2022

Abstract Alzheimer disease (AD) is the leading cause of dementia that affects millions old people. Despite significant advances in understanding AD pathobiology, no modifying treatment available. MicroRNA‐124 (miR‐124) most abundant miRNA normal brain with great potency to ameliorate AD‐like pathology, while it deficient brain. Herein, authors develop a DNA nanoflowers (DFs)‐based delivery system realize exogenous supplementation miR‐124 for therapy. The DFs well‐controlled size and morphology are prepared, chimera attached via hybridization. further modified RVG29 peptide simultaneously brain‐blood barrier (BBB) penetration neuron targeting. Meanwhile, Rutin, small molecular ancillary drug, co‐loaded into structure its intercalation double stranded region. Interestingly, Rutin could synergize suppress expression both BACE1 APP, thus achieving robust inhibition amyloid β generation. nanosystem pro‐long circulation vivo, promote BBB targeting, resulting increase hippocampus APP/PS1 mice therapeutic efficacy vivo. Such bio‐derived shows promise as biocompatible nanomedicine

Language: Английский

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Functionalization strategies of polymeric nanoparticles for drug delivery in Alzheimer’s disease: Current trends and future perspectives

Frontiers in Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Aug. 4, 2022

Alzheimer's disease (AD), the most common form of dementia, is a progressive and multifactorial neurodegenerative disorder whose primary causes are mostly unknown. Due to increase in life expectancy world population, including developing countries, AD, incidence rises dramatically with age, at forefront among diseases. Moreover, definitive cure not yet within reach, imposing substantial medical public health burdens every latitude. Therefore, effort devise novel effective therapeutic strategies still paramount importance. Genetic, functional, structural biochemical studies all indicate that new efficacious drug delivery interfere different levels various cellular molecular targets. Over last few decades, development nanomedicine preclinical stage has shown progress fast pace, thus paving way for its potential impact on human improving prevention, diagnosis, treatment age-related disorders, AD. Clinical translation nano-based therapeutics, despite current limitations, may present important advantages innovation be exploited neuroscience field as well. In this state-of-the-art review article, we promising applications polymeric nanoparticle-mediated bypassing blood-brain barrier AD models boost pharmacological safety efficacy. particular, strategic chemical functionalization nanocarriers could successfully employed treating thoroughly described. Emphasis also placed nanotheranostics both diagnostic tool targeted treatments. Our highlights emerging role management providing readers an overview nanostrategies currently available develop future against chronic disease.

Language: Английский

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Extracellular vesicles, the emerging mirrors of brain physiopathology

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(3), P. 721 - 743

Published: Jan. 1, 2023

Extracellular vesicles are secreted by a wide variety of cells, and their primary functions include intercellular communication, immune responses, human reproduction, synaptic plasticity.Their molecular cargo reflects the physiological processes that cells origin undergoing.Thus, many studies have suggested extracellular could be promising biomarker tool for diseases, mainly due to biological relevance easy accessibility broad range body fluids.Moreover, since composition leads them cross blood-brain barrier bidirectionally, growing evidence points as emerging mirrors brain diseases processes.In this regard, review explores biogenesis vesicles, role in different pathological processes, potential clinical practice, recent outstanding about exosomes major such Alzheimer's disease (AD), Parkinson's (PD), multiple sclerosis (MS), amyotrophic lateral (ALS), or tumors.

Language: Английский

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Nano biomaterials based strategies for enhanced brain targeting in the treatment of neurodegenerative diseases: an up-to-date perspective

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Dec. 13, 2023

Neurons and their connecting axons gradually degenerate in neurodegenerative diseases (NDs), leading to dysfunctionality of the neuronal cells eventually death. Drug delivery for treatment effected nervous system is notoriously complicated because presence natural barriers, i.e., blood-brain barrier blood cerebrospinal fluid barrier. Palliative care currently standard many diseases. Therefore, programs that target disease's origin rather than its symptoms are recommended. Nanotechnology-based drug platforms offer an innovative way circumvent these obstacles deliver medications directly central system, thereby enabling several common neurological problems, Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis. Interestingly, combination nanomedicine gene therapy enables targeting selective mutant genes responsible progression NDs, which may provide a much-needed boost struggle against Herein, we discussed various obstacles, followed by detailed insight into recently developed techniques restore function via differentiation neural stem cells. Moreover, comprehensive background on role controlling neurogenesis explained. Additionally, numerous phytoconstituents with neuroprotective properties molecular targets identification management NDs also deliberated. Furthermore, ongoing clinical trials marketed products provided this manuscript.

Language: Английский

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Exosomes-Based Nanomedicine for Neurodegenerative Diseases: Current Insights and Future Challenges

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(1), P. 298 - 298

Published: Jan. 16, 2023

Neurodegenerative diseases constitute a group of pathologies whose etiology remains unknown in many cases, and there are no treatments that stop the progression such diseases. Moreover, existence blood–brain barrier is an impediment to penetration exogenous molecules, including those found drugs. Exosomes extracellular vesicles secreted by wide variety cells, their primary functions include intercellular communication, immune responses, human reproduction, synaptic plasticity. Due natural origin molecular similarities with most cell types, exosomes have emerged as promising therapeutic tools for numerous Specifically, neurodegenerative shown be potential target this nanomedicine strategy due difficult access brain strategy’s pathophysiological complexity. In regard, review explores important biological-origin drug delivery systems, innovative isolation methods exosomes, physicochemical characterization, loading, cutting-edge functionalization strategies them within brain, latest research studies diseases, future challenges nanomedicine-based tools.

Language: Английский

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Identification of disulfidptosis-related genes and subgroups in Alzheimer’s disease

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Aug. 4, 2023

Background Alzheimer’s disease (AD), a common neurological disorder, has no effective treatment due to its complex pathogenesis. Disulfidptosis, newly discovered type of cell death, seems be closely related the occurrence various diseases. In this study, through bioinformatics analysis, expression and function disulfidptosis-related genes (DRGs) in were explored. Methods Differential analysis was performed on gene matrix AD, intersection differentially expressed AD obtained. Hub further screened using multiple machine learning methods, predictive model constructed. Finally, 97 samples divided into two subgroups based hub genes. Results total 22 overlapping identified, 7 obtained learning, including MYH9, IQGAP1, ACTN4, DSTN, ACTB, MYL6, GYS1. Furthermore, diagnostic capability validated external datasets clinical samples. Based these genes, constructed, with large area under curve (AUC = 0.8847), AUCs validation also higher than 0.7, indicating high accuracy model. Using unsupervised clustering Cluster1 ( n 24) Cluster2 73), most at levels Cluster2. Immune infiltration revealed that had level immune scores. Conclusion A close association between disulfidptosis established assess risk subtype patients. This study provides new perspectives for exploring biomarkers potential therapeutic targets disease.

Language: Английский

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Neuromodulation by nanozymes and ultrasound during Alzheimer’s disease management

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

Published: March 30, 2024

Language: Английский

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