Tau seed amplification assay reveals relationship between seeding and pathological forms of tau in Alzheimer’s disease brain DOI Creative Commons
Bryan Frey,

David Holzinger,

Keenan C. Taylor

и другие.

Acta Neuropathologica Communications, Год журнала: 2023, Номер 11(1)

Опубликована: Ноя. 14, 2023

Abstract Tau seed amplification assays (SAAs) directly measure the seeding activity of tau and would therefore be ideal biomarkers for clinical trials targeting seeding-competent in Alzheimer’s disease (AD). However, precise relationship between measured by SAA levels pathological forms AD brain remains unknown. We developed a new based on full-length 0N3R with sensitivity low fg/ml range used it to characterize 103 samples from three independent cohorts. clearly discriminated control samples. Interestingly, was absent Progressive Supranuclear Palsy (PSP) putamen, suggesting that our did not amplify 4R aggregates PSP brain. The specificity further supported analysis matched hippocampus cerebellum While detected Braak stages I-II, no present is devoid inclusions. Analysis 40 middle frontal gyrus encompassing all showed gradually increased stage. This presence inclusions robust correlations results phosphorylated tau212/214, tau181, aggregated tau, sarkosyl-insoluble tau. Strikingly, we already at stage II-III, can detect pathology earlier than conventional immunohistochemical staining. In conclusion, data suggest quantitative human provides an important basis development accessible

Язык: Английский

Synaptic degeneration in Alzheimer disease DOI
Makis Tzioras, Robert I. McGeachan, Claire S. Durrant

и другие.

Nature Reviews Neurology, Год журнала: 2022, Номер 19(1), С. 19 - 38

Опубликована: Дек. 13, 2022

Язык: Английский

Процитировано

267

Recent advances in molecular pathways and therapeutic implications targeting neuroinflammation for Alzheimer’s disease DOI Open Access

Rishika Dhapola,

Subhendu Shekhar Hota,

Phulen Sarma

и другие.

Inflammopharmacology, Год журнала: 2021, Номер 29(6), С. 1669 - 1681

Опубликована: Ноя. 23, 2021

Язык: Английский

Процитировано

252

Neuroinflammation: A Potential Risk for Dementia DOI Open Access
Md Afroz Ahmad, Ozaifa Kareem,

Mohammad Khushtar

и другие.

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(2), С. 616 - 616

Опубликована: Янв. 6, 2022

Dementia is a neurodegenerative condition that considered major factor contributing to cognitive decline reduces independent function. Pathophysiological pathways are not well defined for diseases such as dementia; however, published evidence has shown the role of numerous inflammatory processes in brain toward their pathology. Microglia central nervous system (CNS) principal components brain’s immune defence and can detect harmful or external pathogens. When stimulated, cells trigger neuroinflammatory responses by releasing proinflammatory chemokines, cytokines, reactive oxygen species, nitrogen species order preserve cell’s microenvironment. These markers include cytokines IL-1, IL-6, TNFα chemokines CCR3 CCL2 CCR5. Microglial may produce prolonged response that, some circumstances, indicated promotion diseases. The present review focused on involvement microglial cell activation throughout conditions link between dementia.

Язык: Английский

Процитировано

95

The Amyloid-Beta Clearance: From Molecular Targets to Glial and Neural Cells DOI Creative Commons
Wenjun Cai, Tong Wu, Ning Chen

и другие.

Biomolecules, Год журнала: 2023, Номер 13(2), С. 313 - 313

Опубликована: Фев. 7, 2023

The deposition of amyloid-beta (Aβ) plaques in the brain is one primary pathological characteristics Alzheimer’s disease (AD). It can take place 20–30 years before onset clinical symptoms. imbalance between production and clearance Aβ major causes AD. Enhancing at an early stage attractive preventive therapeutic strategy Direct inhibition aggregation using small molecules, peptides, monoclonal antibody drugs has not yielded satisfactory efficacy trials for decades. Novel approaches are required to understand combat deposition. Neurological dysfunction a complex process that integrates functions different types cells brain. role non-neurons AD been fully elucidated. An in-depth understanding interactions neurons contribute elucidation formation identification effective drug targets. patient-derived pluripotent stem (PSCs) contain complete background information have potential differentiate into various vitro, which may bring new insight treatment Here, we systematically review latest studies on clarify roles cell among microglia, astroglia response plaques, will be beneficial explore methods reconstructing models inducible PSCs (iPSCs) through differentiation techniques validating applications plaques. This provide most promising directions finding clues preventing delaying development

Язык: Английский

Процитировано

30

8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases DOI Creative Commons
Damijan Knez, Daniel Diez‐Iriepa, Mourad Chioua

и другие.

Acta Pharmaceutica Sinica B, Год журнала: 2023, Номер 13(5), С. 2152 - 2175

Опубликована: Янв. 19, 2023

We describe the development of quinolylnitrones (QNs) as multifunctional ligands inhibiting cholinesterases (ChEs: acetylcholinesterase and butyrylcholinesterase-hBChE) monoamine oxidases (hMAO-A/B) for therapy neurodegenerative diseases. identified QN 19, a simple, low molecular weight nitrone, that is readily synthesized from commercially available 8-hydroxyquinoline-2-carbaldehyde. Quinolylnitrone 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition, yet unexpectedly showed potent inhibition hBChE (IC50 = 1.06 ± 0.31 nmol/L) hMAO-B 4.46 0.18 μmol/L). The crystal structures with provided structural basis binding, which was further studied by enzyme kinetics. Compound acted free radical scavenger biometal chelator, crossed blood-brain barrier, not cytotoxic, neuroprotective properties in 6-hydroxydopamine cell model Parkinson's disease. In addition, vivo studies anti-amnesic effect scopolamine-induced mouse AD without adverse effects on motoric function coordination. Importantly, chronic treatment double transgenic APPswe-PS1δE9 mice reduced amyloid plaque load hippocampus cortex female mice, underscoring disease-modifying 19.

Язык: Английский

Процитировано

27

Molecular mechanisms and therapeutic potential of icariin in the treatment of Alzheimer's disease DOI
Lingyan Zheng,

Sichen Wu,

Haichao Jin

и другие.

Phytomedicine, Год журнала: 2023, Номер 116, С. 154890 - 154890

Опубликована: Май 20, 2023

Язык: Английский

Процитировано

25

Navigating the dementia landscape: Biomarkers and emerging therapies DOI

Shubhrat Maheshwari,

Aditya Singh, Valeed Ahmad Ansari

и другие.

Ageing Research Reviews, Год журнала: 2024, Номер 94, С. 102193 - 102193

Опубликована: Янв. 10, 2024

Язык: Английский

Процитировано

16

Design, Current States, and Challenges of Nanomaterials in Anti-Neuroinflammation: A Perspective on Alzheimer’s Disease DOI

Xinyang Hong,

Tongkai Chen, Yunyun Liu

и другие.

Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102669 - 102669

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1

Development of the “hidden” multi-target-directed ligands by AChE/BuChE for the treatment of Alzheimer's disease DOI
Rui Chen, Xinjuan Li, Hongsong Chen

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 251, С. 115253 - 115253

Опубликована: Март 10, 2023

Язык: Английский

Процитировано

22

Mulberry Leaf Compounds and Gut Microbiota in Alzheimer’s Disease and Diabetes: A Study Using Network Pharmacology, Molecular Dynamics Simulation, and Cellular Assays DOI Open Access
Xue Bai, Xinyi Zhao, Kaifeng Liu

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 4062 - 4062

Опубликована: Апрель 5, 2024

Recently, studies have reported a correlation that individuals with diabetes show an increased risk of developing Alzheimer’s disease (AD). Mulberry leaves, serving as both traditional medicinal herb and food source, exhibit significant hypoglycemic antioxidative properties. The flavonoid compounds in mulberry leaf offer therapeutic effects for relieving diabetic symptoms providing neuroprotection. However, the mechanisms this effect not been fully elucidated. This investigation aimed to investigate combined specific flavonoids (kaempferol, quercetin, rhamnocitrin, tetramethoxyluteolin, norartocarpetin) on type 2 mellitus (T2DM) AD. Additionally, role gut microbiota these two diseases’ treatment was studied. Using network pharmacology, we investigated potential microbiota, combating AD T2DM. In addition, identified protein tyrosine phosphatase 1B (PTP1B) key target kaempferol diseases. Molecular docking molecular dynamics simulations showed has inhibit PTP1B indirect AD, which proven by measuring IC50 (279.23 μM). cell experiment also confirmed dose-dependent phosphorylation total cellular HepG2 cells. research supports concept food–medicine homology broadens range medical treatments highlighting prospect integrating herbal remedies modern research.

Язык: Английский

Процитировано

8