Comparative Clinical Pathology, Год журнала: 2024, Номер unknown
Опубликована: Сен. 13, 2024
Язык: Английский
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(10), С. 5122 - 5122
Опубликована: Май 8, 2024
While primarily produced in the pineal gland, melatonin's influence goes beyond its well-known role regulating sleep, nighttime metabolism, and circadian rhythms, field of chronobiology. A plethora new data demonstrates melatonin to be a very powerful molecule, being potent ROS/RNS scavenger with anti-inflammatory, immunoregulatory, oncostatic properties. Melatonin metabolites exert multiple beneficial effects cutaneous systemic aging. This review is focused on neuroprotective during has an anti-aging capacity, retarding rate healthy brain aging development age-related neurodegenerative diseases, such as Alzheimer's disease, Parkinson's Huntington's sclerosis, amyotrophic lateral etc. Melatonin, well metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) N1-acetyl-5-methoxykynuramine (AMK), can reduce oxidative damage by shielding mitochondria from dysfunction process. could also implicated treatment conditions, modifying their characteristic low-grade neuroinflammation. It either prevent initiation inflammatory responses or attenuate ongoing inflammation. Drawing current knowledge, this discusses potential benefits supplementation preventing managing cognitive impairment diseases.
Язык: Английский
Процитировано
14
Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102481 - 102481
Опубликована: Сен. 3, 2024
Alzheimer's disease (AD) is the most common cause of dementia and accounts for 60-70 % all cases. It affects millions people worldwide. AD poses a substantial economic burden on societies healthcare systems. progressive neurodegenerative disorder characterized by cognitive decline, memory loss, impaired daily functioning. As prevalence continues to increase, understanding its pathogenesis, improving diagnostic methods, developing effective therapeutics have become paramount. This comprehensive review delves into intricate mechanisms underlying AD, explores current state techniques, examines emerging therapeutic strategies. By revealing complexities this aims contribute growing body knowledge surrounding devastating disease.
Язык: Английский
Процитировано
13
Ageing Research Reviews, Год журнала: 2024, Номер 96, С. 102286 - 102286
Опубликована: Март 30, 2024
Язык: Английский
Процитировано
12
NeuroImmune Pharmacology and Therapeutics, Год журнала: 2025, Номер unknown
Опубликована: Фев. 8, 2025
Abstract Objectives Amyloid-β (Aβ) plaque deposition in the brain is a principal pathological feature of both Alzheimer’s disease (AD) and progressive human immunodeficiency virus type one (HIV-1) infection. Both enable Aβ assembly protein aggregation. The potential link between HIV-1 AD remains uncertain, supporting need for reliable animal model. tropic pathogenic humans. It does not replicate mice. restricted species tropism has slowed progress basic research activities. current study seeks to correct model limitations. Methods We created an mouse address develop small that allows studies viral infection by making knock-in (KI) with amyloid precursor (APP) KM670,671NL Swedish mutation genome. resulting founder mice were crossed immunodeficient NOG (NOD. Cg- Prkdc scid Il2rg tm1Sug Tg(CMV -IL-34 ) 1 /Jic) generate NOG/APP /IL-34 (NAIL) reconstituted hematopoietic stem cells NAIL functional adaptive innate immune systems. Four-month-old, humanized infected ADA , macrophage-tropic strain then evaluated pathology. Results Productive was confirmed plasma RNA levels load increased tenfold day 10 25 post-infection. By 25, DNA establishment reservoirs CD45+ from tissues Additionally, p24 measurements lymphoid validated productive Amyloid burden increased. Immunofluorescence staining revealed co-localization fibrils HLA-DR + microglia Conclusions These results highlight AD-HIV model’s unique pathobiological infectious features where responses can now be measured.
Язык: Английский
Процитировано
1
Phytomedicine, Год журнала: 2025, Номер unknown, С. 156502 - 156502
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
1
Journal of dementia and Alzheimer's disease, Год журнала: 2025, Номер 2(1), С. 2 - 2
Опубликована: Янв. 10, 2025
Alzheimer’s disease (AD) is the most common cause of dementia, and no cure currently available. The β-amyloid cascade AD neurofibrillary tangles are basis current understanding pathogenesis, driving drug investigation other discoveries. Up until now, models have entirely validated hypothesis. must be capable recapitulating critical events this pathology, including plaques tangles. development probably derived from amyloid precursor protein (APP) presenilin 1 (PS1) familial (FAD) mutations, while tangle-like pathology determined by tau mutations. Transgenic mouse struggle to replicate entire spectrum AD, particularly neuronal death stemming pathologies. Furthermore, success these transgenic mice often relies on overexpression APP transgenes enclosing FAD-associated mutations at levels beyond physiological. Ultimate species-specific discrepancies in genome composition between human may hinder accurate recapitulation pathological models. Although none fully mirrors experimental vivo animal provided valuable insights into toxicity overall pathophysiological AD. Therefore, been widely used preclinical evaluation therapeutic strategies played a pivotal role immunotherapies for In review, we sum up main research, whether they mutation-based mice, plus or mice. specific characteristics each model significance their use focusing advantages disadvantages, as well progress made forthcoming challenges replicating neurodegenerative disease, also highlighted.
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Янв. 22, 2025
Abstract More than half of epileptic patients ultimately turned to intractable epilepsy. Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), the most common type epilepsies, whose pathological mechanism remains elusive. Here, using 42 human samples from surgical donors MTLE (32 and 10 without HS) through single-cell resolution Stereo-seq histologcial experiments, we revealed spatially changes gene expression cell composition HS systematically. After precise parcellation subregions differentially expressed (DEG) analysis between each region sclerosis, found Cornu Ammonis (CA) higher number DEGs were vulnerable especially CA1 CA3. Within CA1, that CA1-superficial proximal areas more CA1-deep distal in sclerosis. Meanwhile, after analyzing 350,795 segmented cells Stereo-seq, dramatically increasing density astrocyte accompanied significantly decreasing excitatory neurons superficial CA3 In these two subregions, proliferative (P_astrocyte) reactive (R_astrocyte) be enriched whereas apoptotic subtype (A_astrocyte), related pathway, was mainly located alveus, which strengthened communication microglia (R_microglia) HS, revealing novel feature our work. The pseudotime indicated CA underwent synaptic impairment, energy dysfunction, aging, finally losing identity until death autophagy or apoptosis. Besides, also a resilient subtype, EX_CA2-4.3, highly extracellular matrix genes including PDYN , interaction BDNF-NTRK, NFASC-CNTN1 withstand damage Together, study provided reference hippocampus caused by MTLE, highlighted potential on molecular cellular level MTLE-HS.
Язык: Английский
Процитировано
0
Journal of Xenobiotics, Год журнала: 2025, Номер 15(2), С. 50 - 50
Опубликована: Март 30, 2025
Mild cognitive impairment (MCI) is recognized as an intermediate stage between normal aging and dementia. Oxidative stress implicated in the pathophysiology of neurodegenerative diseases, playing a crucial role. This study aimed to investigate differences malondialdehyde (MDA) levels serum cerebrospinal fluid (CSF) patients with MCI compared FDA-approved biomarkers, based on age, sex, education level. Participants aged 55–90 years old were categorized into three groups especially CSF Aβ42/Aβ40 ratio clinical screening assessments: 30 (A+) abnormal ratios (Group A), (A−) B), healthy participants C). The measurements biomarkers performed using automated immunochemical method (Fujirebio, Inc.), while MDA determination was competitive inhibition enzyme immunoassay technique (ELK Biotechnology Co., Ltd.). Our results showed that mean values significantly lower group C than A (83 ng/mL vs. 130 ng/mL, p = 0.024) B 142 0.011), respectively. Differences presented These findings suggest lipid peroxidation, indicated by MDA, could serve potential biomarker for early recognition MCI.
Язык: Английский
Процитировано
0
Aging Cell, Год журнала: 2025, Номер unknown
Опубликована: Янв. 19, 2025
ABSTRACT Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting the elderly. The imbalance of protein production and degradation processes leads to accumulation misfolded abnormally aggregated amyloid‐beta (Aβ) in extracellular space forms senile plaques, which constitute one most critical pathological hallmarks AD. KIF9, member kinesin superfamily, mediates anterograde transport intracellular cargo along microtubules. However, exact role KIF9 AD pathogenesis remains largely elusive. In this study, we reported that expression family 9 (KIF9) hippocampus APP23/PS45 double‐transgenic model mice declined an age‐dependent manner, concurrent with macroautophagy dysfunction. Furthermore, found mediated lysosomes through light chain 1 (KLC1), thereby participating amyloidogenic pathway‐related proteins Aβ precursor (APP) cells promoting pathway. Importantly, genetic upregulation via adeno‐associated virus (AAV) diminished deposition alleviated cognitive impairments by enhancing function. Collectively, our findings underscore ability promote KLC1‐mediated lysosomes, effectively ameliorating dysfunction mice. These discoveries suggest may represent novel therapeutic target for treatment
Язык: Английский
Процитировано
0
Frontiers in Pharmacology, Год журнала: 2025, Номер 16
Опубликована: Янв. 28, 2025
Introduction This study aims to establish the fingerprint spectra of Kai-Xin-San (KXS) and investigate its spectrum-effect relationship in treating Alzheimer’s disease (AD). Methods Initially, fingerprints 15 batches KXS were established analyzed using HPLC, with method’s precision, stability, repeatability thoroughly evaluated. Subsequently, effects assessed an olfactory escape memory experiment, utilizing Aβ 42 transgenic drosophila as a model. Finally, between improvement was analyzed, active ingredients subjected validation testing. Results The results identified seventeen common peaks fingerprint, eight components determined: polygalaxanthone III, 3-6-disinapoylsucrose, ginsenoside Rg1, Rb1, β-asarone, α-asarone, dehydrotumulosic acid, dehydropachymic acid. Treatment (1%, for 4 days) significantly enhanced performance index flies experiment. Both analysis tests indicated that α-asarone positively correlated improved HPLC method demonstrated excellent accuracy, reproducibility, making it suitable quality evaluation control KXS. Polygalaxanthone are potential anti-AD effects. Discussion These findings provide experimental basis developing new drugs based on ingredient combinations.
Язык: Английский
Процитировано
0