Alzheimer’s Disease Immunotherapy and Mimetic Peptide Design for Drug Development: Mutation Screening, Molecular Dynamics, and a Quantum Biochemistry Approach Focusing on Aducanumab::Aβ2–7 Binding Affinity DOI Creative Commons
Victor L. B. França, Eveline M. Bezerra, Roner F. da Costa

и другие.

ACS Chemical Neuroscience, Год журнала: 2024, Номер unknown

Опубликована: Сен. 20, 2024

Seven treatments are approved for Alzheimer's disease, but five of them only relieve symptoms and do not alter the course disease. Aducanumab (Adu) lecanemab novel disease-modifying antiamyloid-β (Aβ) human monoclonal antibodies that specifically target pathophysiology disease (AD) were recently its treatment. However, their administration is associated with serious side effects, use limited to early stages Therefore, drug discovery remains great importance in AD research. To gain new insights into development drugs a combination techniques was employed, including mutation screening, molecular dynamics, quantum biochemistry. These used outline interfacial interactions Aducanumab::Aβ

Язык: Английский

Oxygen metabolism abnormality and Alzheimer's disease: An update DOI Creative Commons
Guangdong Liu, Cui Yang,

Xin Wang

и другие.

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

Процитировано

25
Review on anti-alzheimer drug development: approaches, challenges and perspectives DOI Creative Commons
Abdallah E. Abdallah

RSC Advances, Год журнала: 2024, Номер 14(16), С. 11057 - 11088

Опубликована: Янв. 1, 2024

Alzheimer has many crucial factors that should be considered in order to get better results from clinical trials. Benzimidazole and its isosteres represent significant scaffolds for designing potential multi-target anti-alzheimer molecules.

Язык: Английский

Процитировано

15
Brain Microenvironment-Remodeling Nanomedicine Improves Cerebral Glucose Metabolism, Mitochondrial Activity and Synaptic Function in A Mouse Model of Alzheimer’s Disease DOI Creative Commons
Elliya Park, Chunsheng He, Azhar Z. Abbasi

и другие.

Biomaterials, Год журнала: 2025, Номер unknown, С. 123142 - 123142

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
Approved drugs and natural products at clinical stages for treating Alzheimer’s disease DOI

Yajing Ma,

Sufang Liu,

Qingfeng Zhou

и другие.

Chinese Journal of Natural Medicines, Год журнала: 2024, Номер 22(8), С. 699 - 710

Опубликована: Авг. 1, 2024

Язык: Английский

Процитировано

7
Constituents, pharmacological activities, pharmacokinetic studies, clinical applications, and safety profile on the classical prescription Kaixinsan DOI Creative Commons
Liping Chen, Lin Jiang,

Xiaoyu Shi

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Фев. 1, 2024

Kaixinsan (KXS) is a noteworthy classical prescription, which consists of four Chinese medicinal herbs, namely Polygalae Radix, Ginseng Radix et Rhizoma, Poria, and Acori Tatarinowii Rhizoma. KXS was initially documented in the ancient book Beiji Qianjin Yaofang written by Sun Simiao Tang Dynasty 652 A.D. As traditional medicine (TCM) it functions to nourish heart replenish Qi, calm tranquilize mind, excrete dampness. Originally used treat amnesia, now also effective memory decline applied depression. Although there remains an abundance literature investigating from multiple aspects, few reviews summarize features research, impedes better exploration exploitation KXS. This article intends comprehensively analyze up-to-date information concerning chemical constituents, pharmacology, pharmacokinetics, clinical applications, safety based on scientific literature, as well examine possible gaps current research tackle issues next step. The constituents primarily consist saponins, xanthones, oligosaccharide esters, triterpenoids, volatile oils, flavonoids. Of these, saponins are predominant active ingredients, increasing evidence has indicated that they exert therapeutic properties against mental disease. Pharmacokinetic illustrated crucial exposed substances rat plasma after administration ginsenoside Re (GRe), Rb1 (GRb1), polygalaxanthone III (POL). provides additional descriptions safety. In this review, highlighted guide further comprehensive other prescriptions.

Язык: Английский

Процитировано

6
The Role of Reactive Oxygen Species in Alzheimer's Disease:from Mechanism to Biomaterials Therapy DOI

Zhuohang Yu,

Feng Luo

Advanced Healthcare Materials, Год журнала: 2024, Номер 13(29)

Опубликована: Март 21, 2024

Alzheimer's disease (AD) is a chronic, insidious, and progressive neurodegenerative that remains clinical challenge for society. The fully approved drug lecanemab exhibits the prospect of therapy against pathological processes, while debatable adverse events conflict with concentration required anticipated therapeutic effects. Reactive oxygen species (ROS) are involved in progression AD, as has been demonstrated much research regarding oxidative stress (OS). contradiction between dosage event may be resolved through targeted transport by biomaterials get effects via regulation ROS. Besides, fix delivery issues promoting penetration drugs across blood-brain barrier (BBB), protecting from peripheral degradation, elevating bioavailability. goal to comprehensively understand mechanisms ROS AD potential ROS-related treatment AD. This review focuses on OS its connection novel recent years inspire biomaterial development. Revisiting these associated thorough investigations presents considerable bright future improving effective interventions

Язык: Английский

Процитировано

6
Neuropsychological Assessment for Early Detection and Diagnosis of Dementia: Current Knowledge and New Insights DOI Open Access
Patricia Alzola, Cristóbal Carnero Pardo, Félix Bermejo‐Pareja

и другие.

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(12), С. 3442 - 3442

Опубликована: Июнь 12, 2024

Dementia remains an underdiagnosed syndrome, and there is a need to improve the early detection of cognitive decline. This narrative review examines role neuropsychological assessment in characterization changes associated with dementia syndrome at different states. The first section describes indicators decline major barriers their identification. Further, optimal screening conditions most widely accepted tests are described. second analyzes main differences performance between Alzheimer’s disease other subtypes dementia. Finally, current challenges aging/dementia future approaches discussed. Essentially, we find that research beginning uncover precede dementia, while continuing refine differential diagnosis neurodegenerative disorders cause However, neuropsychology faces several barriers, including cultural diversity populations, limited implementation public health systems, adaptation technological advances. Nowadays, plays fundamental characterizing stages but more efforts needed develop harmonized procedures facilitate its use clinical contexts protocols.

Язык: Английский

Процитировано

6
Predicting Alzheimer's disease CSF core biomarkers: a multimodal Machine Learning approach DOI Creative Commons
Anna Michela Gaeta,

María Quijada-López,

Ferrán Barbé

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 16

Опубликована: Июнь 26, 2024

Introduction Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Current core cerebrospinal fluid (CSF) AD biomarkers, widely employed for diagnosis, require lumbar puncture to be performed, making them impractical as screening tools. Considering the role of sleep disturbances in AD, recent research suggests quantitative electroencephalography features potential non-invasive biomarkers pathology. However, analysis comprehensive polysomnography (PSG) signals remains relatively understudied. PSG test enabling qualitative and wide range parameters, offering additional insights alongside other biomarkers. Machine Learning (ML) gained interest its ability discern intricate patterns within complex datasets, promise neuropathology detection. Therefore, this study aims evaluate effectiveness multimodal ML approach predicting CSF Methods Mild-moderate patients were prospectively recruited PSG, followed by testing blood samples underwent preprocessing extract non-linear, time domain frequency statistics features. Multiple algorithms trained using four subsets input features: clinical variables (CLINVAR), conventional parameters (SLEEPVAR), signal (PSGVAR) combination all (ALL). Cross-validation techniques model performance ensure generalizability. Regression models developed determine most effective variable combinations explaining variance Results On 49 subjects, Gradient Boosting Regressors achieved best results estimating levels, different loss functions each biomarker: least absolute deviation (LAD) A β 42, squares (LS) p -tau Huber t -tau. The ALL subset demonstrated lowest training errors three albeit with varying performance. Specifically, SLEEPVAR yielded while accurately predicted due errors. Conclusions Multimodal can help predict outcome early utilizing economically feasible variables. integration computational into medical practice offers promising tool at risk potentially guiding decisions.

Язык: Английский

Процитировано

6
New Garden Rose (Rosa × hybrida) Genotypes with Intensely Colored Flowers as Rich Sources of Bioactive Compounds DOI Creative Commons
Nataša Simin, Nemanja Živanović,

Biljana Božanić Tanjga

и другие.

Plants, Год журнала: 2024, Номер 13(3), С. 424 - 424

Опубликована: Янв. 31, 2024

Garden roses, known as Rosa × hybrida, hold a prominent position one of the most important and economically valuable plants in horticulture. Additionally, their products—essential oil, rose water, concrete, concentrate—find extensive use cosmetic, pharmaceutical, food industries, due to specific fragrances potential health benefits. Rose flowers are rich biologically active compounds, such phenolics, flavonoids, anthocyanins, carotenoids. This study aims investigate five new garden genotypes with intensely colored serve sources compounds. Phenolic profile was evaluated by determination total phenolic (TPC), flavonoid (TFC), monomeric anthocyanins (TAC) contents LC-MS/MS analysis selected Antioxidant activity via DPPH FRAP assays, neuroprotective acethylcholinesterase inhibition assay, antidiabetic viaα-amylase α-glucosidase assays. The investigated were phenolics (TPC varied from 148 260 mg galic acid eq/g de, TFC 19.9 59.7 quercetin TAC 2.21 13.1 cyanidin 3-O-glucoside de). Four out had higher TPC than extract R. damascene, famous cultivar. dominant flavonoids all glycosides kaempferol. extracts showed high antioxidant comparable synthetic BHT, very inhibitory potential, moderate activity, low inhibit α-amylase.

Язык: Английский

Процитировано

5
Novel Therapeutic Strategies in Alzheimer’s Disease: Pitfalls and Challenges of Anti-Amyloid Therapies and Beyond DOI Open Access
Giacomo Tondo, Fabiola De Marchi,

Francesca Bonardi

и другие.

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(11), С. 3098 - 3098

Опубликована: Май 25, 2024

Alzheimer's disease (AD) causes a significant challenge to global healthcare systems, with limited effective treatments available. This review examines the landscape of novel therapeutic strategies for AD, focusing on shortcomings traditional therapies against amyloid-beta (Aβ) and exploring emerging alternatives. Despite decades research emphasizing role Aβ accumulation in AD pathogenesis, clinical trials targeting have obtained disappointing results, highlighting complexity pathophysiology need investigating other approaches. In this manuscript, we first discuss challenges associated anti-Aβ therapies, including efficacy potential adverse effects, underscoring necessity alternative mechanisms targets. Thereafter, promising non-Aβ-based strategies, such as tau-targeted neuroinflammation modulation, gene stem cell therapy. These approaches offer new avenues treatment by addressing additional pathological hallmarks downstream effects beyond deposition.

Язык: Английский

Процитировано

5