Prescriber, Journal Year: 2023, Volume and Issue: 34(7), P. 15 - 18
Published: July 1, 2023
New effective treatments for Alzheimer's disease have eluded researchers many years, but promising pharmacotherapies may at last be approaching clinical approval. This article examines some of these new treatments, their modes action and the practicalities implementation once they reach market.
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: Aug. 23, 2024
Abstract Alzheimer’s disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate diverse, stemming from a combination factors such aging, genetics, environment. Our current understanding AD pathologies involves various hypotheses, cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, abnormal autophagy. Nonetheless, unraveling interplay among these pathological aspects pinpointing primary initiators require further elucidation validation. In past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available primarily offer symptomatic relief often accompanied by undesirable side However, recent approvals aducanumab ( 1 ) lecanemab 2 Food Drug Administration (FDA) present potential in disrease-modifying Nevertheless, long-term efficacy safety need Consequently, quest for safer more effective persists formidable pressing task. This review discusses pathogenesis, advances diagnostic biomarkers, latest updates trials, emerging technologies drug development. We highlight progress discovery selective inhibitors, dual-target allosteric modulators, covalent proteolysis-targeting chimeras (PROTACs), protein-protein interaction (PPI) modulators. goal provide insights into prospective development application novel drugs.
Language: Английский
Citations
173
Advanced Science, Journal Year: 2024, Volume and Issue: 11(24)
Published: April 22, 2024
Abstract The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane‐coated nanoparticles derived from different types can mimic surface properties and functionalities source cells, further enhancing their targeting precision efficacy. Neuroinflammation has been increasingly recognized as a critical factor in pathogenesis various NDs, especially Alzheimer's disease (AD). In this study, novel membrane coating is designed by hybridizing platelets chemokine (C–C motif) receptor 2 (CCR2) cells are overexpressed to cross BBB target neuroinflammatory lesions. Past unsuccessful endeavors AD drug development underscore challenge achieving favorable outcomes when utilizing single‐mechanism drugs.Two with mechanisms actions into liposomes successfully loaded realize multitargeting treatment. transgenic mouse model familial (5xFAD), administration these drug‐loaded hybrid results significant reduction amyloid plaque deposition, neuroinflammation, cognitive impairments. Collectively, nanomaterials offer new opportunities precise delivery disease‐specific targeting, which represent versatile platform targeted therapy AD.
Language: Английский
Citations
15
Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(15)
Published: Feb. 22, 2024
Abstract Amyloid beta‐protein (AβA β ) is a main hallmark of Alzheimer's disease (AD), and low amount Aβ protein accumulation appears to be potential marker for AD. Here, an electrochemical DNA biosensor based on polyamide/polyaniline carbon nanotubes (PA/PANI‐CNTs) developed with the aim diagnosing AD early using simple, low‐cost, accessible method rapidly detect Aβ42 in human blood. Electrospun PA nanofibers served as skeleton successive situ deposition PANI CNTs, which contribute both high conductivity abundant binding sites aptamers. After aptamers are immobilized, this aptasensor exhibits precise specific detection blood within only 4 min extremely fast response rate, lower limit, excellent linear range. These findings make significant contribution advancing development serum‐based techniques Aβ42, thereby paving way improved diagnostic capabilities field
Language: Английский
Citations
12
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14
Published: Nov. 8, 2023
Life expectancy is increasing throughout the world and coincides with a rise in non-communicable diseases (NCDs), especially for metabolic disease that includes diabetes mellitus (DM) neurodegenerative disorders. The debilitating effects of disorders influence entire body significantly affect nervous system impacting greater than one billion people disability peripheral as well cognitive loss, now seventh leading cause death worldwide. Metabolic disorders, such DM, neurologic remain significant challenge treatment care individuals since present therapies may limit symptoms but do not halt overall progression. These clinical challenges to address interplay between warrant innovative strategies can focus upon underlying mechanisms aging-related oxidative stress, cell senescence, death. Programmed pathways involve autophagy, apoptosis, ferroptosis, pyroptosis play critical role oversee processes include insulin resistance, β-cell function, mitochondrial integrity, reactive oxygen species release, inflammatory activation. silent mating type information regulation 2 homolog 1
Language: Английский
Citations
20
TrAC Trends in Analytical Chemistry, Journal Year: 2024, Volume and Issue: 172, P. 117546 - 117546
Published: Jan. 17, 2024
Language: Английский
Citations
5
Bioengineering, Journal Year: 2023, Volume and Issue: 10(7), P. 871 - 871
Published: July 23, 2023
Almost three million individuals suffer from multiple sclerosis (MS) throughout the world, a demyelinating disease in nervous system with increased prevalence over last five decades, and is now being recognized as one significant etiology of cognitive loss dementia. Presently, modifying therapies can limit rate relapse potentially reduce brain volume patients MS, but unfortunately cannot prevent progression or onset disability. Innovative strategies are therefore required to address areas inflammation, immune cell activation, survival that involve novel pathways programmed death, mammalian forkhead transcription factors (FoxOs), mechanistic target rapamycin (mTOR), AMP activated protein kinase (AMPK), silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), associated apolipoprotein E (APOE-ε4) gene severe acute respiratory syndrome coronavirus (SARS-CoV-2). These intertwined at levels metabolic oversight cellular metabolism dependent upon nicotinamide adenine dinucleotide (NAD+). Insight into mechanisms these provide new avenues discovery for therapeutic treatment dementia cognition occurs during MS.
Language: Английский
Citations
11
Cells, Journal Year: 2023, Volume and Issue: 12(22), P. 2595 - 2595
Published: Nov. 9, 2023
Metabolic disorders and diabetes (DM) impact more than five hundred million individuals throughout the world are insidious in onset, chronic nature, yield significant disability death. Current therapies that address nutritional status, weight management, pharmacological options may delay but cannot alter disease course or functional organ loss, such as dementia degeneration of systemic bodily functions. Underlying these challenges onset aging associated with increased lifespan, telomere dysfunction, oxidative stress generation lead to multi-system dysfunction. These hurdles point urgent need underlying mechanisms innovative applications. New treatment strategies involve non-coding RNA pathways microRNAs (miRNAs) circular ribonucleic acids (circRNAs), Wnt signaling, Wnt1 inducible signaling pathway protein 1 (WISP1) dependent upon programmed cell death pathways, cellular metabolic AMP-activated kinase (AMPK) nicotinamide, growth factor Non-coding RNAs, AMPK cornerstone for overseeing complex offer avenues DM will necessitate continued appreciation ability each independently unison influence clinical outcome.
Language: Английский
Citations
11
Computers in Biology and Medicine, Journal Year: 2025, Volume and Issue: 186, P. 109607 - 109607
Published: Jan. 1, 2025
Language: Английский
Citations
0
Neurological Sciences, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 20, 2025
Language: Английский
Citations
0
Clinical Chemistry and Laboratory Medicine (CCLM), Journal Year: 2025, Volume and Issue: unknown
Published: March 18, 2025
Abstract Objectives Human tear analysis holds promise for biomarker discovery, but its clinical utility is hindered by the lack of standardized reference values, limiting interindividual comparisons. This study aimed at developing a protocol normalizing metabolomic data from human tears, enhancing potential identification. Methods Tear profiling was conducted on 103 donors (64 females, 39 males, aged 18–82 years) without ocular pathology, using AbsoluteIDQ™ p180 Kit targeted metabolomics. A predictive normalization model incorporating age, sex, and fasting time developed to correct variability. Key metabolites six compound families (amino acids, biogenic amines, acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, sphingomyelins) were identified as references. The approach validated Linear Discriminant Analysis (LDA) test ability classify donor sex based metabolite concentrations. Results Metabolite concentrations exhibited significant model, which predicted “concomitant” each family, successfully reduced this Using ratio observed-to-predicted concentrations, enabled robust comparisons across individuals. LDA classification acylcarnitine C4 achieved 78 % accuracy, correctly identifying 92 female donors. outperformed traditional statistical machine learning methods (Lasso logistic regression Random Forest classification) in discrimination Conclusions novel significantly improves reliability metabolomics enabling facilitates discovery mitigating variability may be extended other biological fluids, applicability precision medicine.
Language: Английский
Citations
0