Pro-cognitive Effects of Dual Tacrine Derivatives Acting as Cholinesterase Inhibitors and NMDA Receptor Antagonists DOI Creative Commons
Markéta Chvojková, David Kolář,

Katarina Kovacova

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 20, 2024

Abstract Therapeutic options for Alzheimer’s disease are limited. Dual compounds targeting two pathophysiological pathways concurrently may enable enhanced effect. The study focuses on tacrine derivatives acting as acetylcholinesterase (AChE) inhibitors and simultaneously subunit-dependent N-methyl-D-aspartate (NMDA) receptor antagonists. Compounds with balanced inhibitory potencies target proteins (K1578 K1599) or increased potency AChE (K1592 K1594) were studied. We aimed to identify the most promising pro-cognitive compound. effects of studied in cholinergic (scopolamine-induced) glutamatergic (MK-801-induced) rat models cognitive deficits Morris water maze. Moreover, effect locomotion open field activity relevant brain structures investigated. compound NMDA receptors was explored by vitro electrophysiology. antagonist scopolamine induced a deficit memory acquisition, however unaffected compounds, reversal learning, that alleviated K1578 K1599. K1599 significantly inhibited striatum, potentially explaining behavioral observations. Glutamatergic dizocilpine (MK-801) which also mitigated MK-801-induced hyperlocomotion field. electrophysiology corroborated K1599-associated emerged compound, demonstrating efficacy both models, consistently intended dual Our findings contributed elucidation structural functional properties associated optimal vivo effects, further research benefit from.

Язык: Английский

Unraveling the role of miRNAs in the diagnosis, progression, and therapeutic intervention of Alzheimer’s disease DOI
Nourhan M. Abdelmaksoud, Al-Aliaa M. Sallam, Ahmed I. Abulsoud

и другие.

Pathology - Research and Practice, Год журнала: 2023, Номер 253, С. 155007 - 155007

Опубликована: Дек. 4, 2023

Язык: Английский

Процитировано

23
Pro-cognitive effects of dual tacrine derivatives acting as cholinesterase inhibitors and NMDA receptor antagonists DOI Open Access
Markéta Chvojková, David Kolář,

Katarina Kovacova

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 176, С. 116821 - 116821

Опубликована: Май 31, 2024

Therapeutic options for Alzheimer's disease are limited. Dual compounds targeting two pathways concurrently may enable enhanced effect. The study focuses on tacrine derivatives inhibiting acetylcholinesterase (AChE) and simultaneously N-methyl-D-aspartate (NMDA) receptors. Compounds with balanced inhibitory potencies the target proteins (K1578 K1599) or increased potency AChE (K1592 K1594) were studied to identify most promising pro-cognitive compound. Their effects in cholinergic (scopolamine-induced) glutamatergic (MK-801-induced) rat models of cognitive deficits Morris water maze. Moreover, impacts locomotion open field activity relevant brain structures investigated. effect compound NMDA receptors was explored by vitro electrophysiology. antagonist scopolamine induced a deficit memory acquisition, however, it unaffected compounds, reversal learning that alleviated K1578 K1599. K1599 significantly inhibited striatum, potentially explaining behavioral observations. dizocilpine (MK-801) which also mitigated MK-801-induced hyperlocomotion field. In patch-clamp corroborated K1599-associated receptor emerged as compound, demonstrating efficacy both models, consistent intended dual We conclude has potential development vivo effects. Our findings contributed elucidation structural functional properties associated optimal efficacy.

Язык: Английский

Процитировано

7
Varenicline Attenuates Memory Impairment in Amyloid-Beta-Induced Rat Model of Alzheimer’s Disease DOI
Seyed Zanyar Athari,

Sareh Kazmi,

Seyed Mehdi Vatandoust

и другие.

Neurochemical Research, Год журнала: 2025, Номер 50(2)

Опубликована: Янв. 27, 2025

Язык: Английский

Процитировано

1
Exploring the parity paradox: Differential effects on neuroplasticity and inflammation by APOEe4 genotype at middle age DOI
Bonnie H. Lee,

Melike Cevizci,

Stephanie E. Lieblich

и другие.

Brain Behavior and Immunity, Год журнала: 2024, Номер 120, С. 54 - 70

Опубликована: Май 19, 2024

Язык: Английский

Процитировано

6
Neuroprotective Potential of Origanum majorana L. Essential Oil Against Scopolamine-Induced Memory Deficits and Oxidative Stress in a Zebrafish Model DOI Creative Commons
Ion Brinza, Răzvan Ştefan Boiangiu, Iasmina Honceriu

и другие.

Biomolecules, Год журнала: 2025, Номер 15(1), С. 138 - 138

Опубликована: Янв. 16, 2025

Origanum majorana L., also known as sweet marjoram, is a plant with multiple uses, both in the culinary field and traditional medicine, because of its major antioxidant, anti-inflammatory, antimicrobial, digestive properties. In this research, we focused on effects O. essential oil (OmEO, at concentrations 25, 150, 300 μL/L), evaluating chemical structure well impact cognitive performance oxidative stress, naive zebrafish (Danio rerio), scopolamine-induced amnesic model (SCOP, 100 μM). The fish behavior was analyzed novel tank-diving test (NTT), Y-maze test, object recognition (NOR) test. We investigated acetylcholinesterase (AChE) activity brain's stress status. parallel, performed silico predictions (research conducted using computational models) pharmacokinetic properties main compounds identified OmEO, platforms such SwissADME, pKCSM, ADMETlab 2.0, ProTox-II. results revealed that were trans-sabinene hydrate (36.11%), terpinen-4-ol (17.97%), linalyl acetate (9.18%), caryophyllene oxide (8.25%), α-terpineol (6.17%). OmEO can enhance memory through AChE inhibition, reduce SCOP-induced anxiety by increasing time spent top zone NTT, significantly markers. These findings underscore potential to improve impairment associated disorders, including Alzheimer's disease (AD).

Язык: Английский

Процитировано

0
Early Spatio-Temporal and Cognitive Deficits in Alzheimer’s Disease DOI Open Access
Tina Iachini, Mariachiara Rapuano, Francesco Ruotolo

и другие.

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(2), С. 579 - 579

Опубликована: Янв. 17, 2025

Background/Objectives: Mental representation of spatial information relies on egocentric (body-based) and allocentric (environment-based) frames reference. Research showed that memory deteriorates as Alzheimer's disease (AD) progresses is among the earliest impaired areas. Most studies have been conducted in static situations despite dynamic nature real-world processing. Thus, this raises question: Does temporal order affect memory? The present study, by adopting a task, explored how item presentation influences judgments individuals with early-stage (eAD) healthy elderly (normal controls-NC). Method: Participants were required to memorize dyads simple 3D geometrical objects presented one at time desk along bar. Afterwards, they had choose what stimulus appeared either closest them (egocentric judgment) or bar (allocentric judgment). Results: Results revealed significantly affected eAD patients but not NC participants. While remain anchored first, which more accurate regardless frame used, are equally appears first second. This presumably because struggle flexibly shift attention update representations situations, leads reliance initial difficulties later. Conclusions: highlights importance further understanding cognitive strategies employed AD patients.

Язык: Английский

Процитировано

0
Asymptomatic neonatal herpes simplex virus infection in mice leads to persistent CNS infection and long-term cognitive impairment DOI Creative Commons
Abigail J. Dutton,

Evelyn M. Turnbaugh,

Chaya Patel

и другие.

PLoS Pathogens, Год журнала: 2025, Номер 21(2), С. e1012935 - e1012935

Опубликована: Фев. 7, 2025

Neonatal herpes simplex virus (nHSV) is a devastating infection impacting approximately 14,000 newborns globally each year. nHSV associated with high neurologic morbidity and mortality, making early intervention critical. Clinical outcomes of symptomatic infections are well-studied, but little known about the frequency of, or following, subclinical asymptomatic nHSV. Given ubiquitous nature HSV shedding in adults, underreported could contribute to long-term neurological damage. To assess potential infection, we developed low-dose (100 PFU) intranasal model neonatal wild-type C57BL/6 mice. At this dose, DNA was detected brain by quantitative PCR (qPCR) not acute clinical signs infection. However, months after inoculation low dose HSV, observed impaired mouse performance on range cognitive memory tests. Memory impairment induced either HSV-1 HSV-2 viruses, indicating that strain-specific. Maternal immunization reduced neonate central nervous system (CNS) viral burden prevented offspring from developing sequelae following Altogether, these results support idea may lead decline adulthood maternal vaccination an effective strategy for reducing infected offspring. These findings have profound implications understanding modeling etiology human neurodegenerative disorders such as Alzheimer's Disease.

Язык: Английский

Процитировано

0
Brain-penetrant histone deacetylase inhibitor RG2833 improves spatial memory in females of an Alzheimer's disease rat model DOI Creative Commons
Kelechi Ndukwe, Peter A. Serrano, Patricia Rockwell

и другие.

Journal of Alzheimer s Disease, Год журнала: 2025, Номер unknown

Опубликована: Фев. 9, 2025

Background Nearly two-thirds of Alzheimer's disease (AD) patients are women. Therapeutics for women critical to lowering their elevated risk developing this major cause adult dementia. Moreover, targeting epigenetic processes such as histone acetylation that regulate multiple cellular pathways is advantageous given the multifactorial nature AD. Histone takes part in memory consolidation, and its disruption linked Objective Determine whether investigational drug RG2833 has repurposing potential a deacetylase HDAC1/3 inhibitor orally bioavailable permeates blood-brain-barrier. Methods effects were determined on cognition, transcriptome, AD-like pathology 11-month TgF344-AD female male rats. Treatment started early course when therapeutic intervention predicted be most effective. Results RG2833-treatment rats: (1) Significantly improved hippocampal-dependent spatial females but not males. (2) Upregulated expression immediate genes, Arc, Egr1 c-Fos, other genes involved synaptic plasticity consolidation females. Remarkably, out 17,168 analyzed each sex, no significant changes gene detected males at p < 0.05, false discovery rate <0.05, fold-change equal or > 1.5. (3) Failed improve amyloid beta accumulation microgliosis Conclusions Our study highlights histone-modifying therapeutics cognitive behavior drive early, especially AD patients.

Язык: Английский

Процитировано

0
Modulation of Cognitive Activity by Plant-Based Extracts (Allium cepa, Coffea robusta, and Brassica oleracea) through the Phosphodiesterase 4B inhibition: Insite from a Mice Model Study DOI Creative Commons
Nazir Ahmad, Kaisun Nesa Lesa, Nanang Fakhrudin

и другие.

Phytomedicine Plus, Год журнала: 2025, Номер unknown, С. 100778 - 100778

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Insights From TgF344-AD, a Double Transgenic Rat Model in Alzheimer’s Disease Research DOI Creative Commons
Andrew Nataraj, Karel Blahna, Karel Ježek

и другие.

Physiological Research, Год журнала: 2025, Номер 1/2025, С. 1 - 17

Опубликована: Март 10, 2025

Alzheimer's disease (AD), a leading cause of dementia worldwide, is multifactorial neurodegenerative disorder characterized by amyloid-beta plaques, tauopathy, neuronal loss, neuro-inflammation, brain atrophy, and cognitive deficits. AD manifests as familial early-onset (FAD) with specific gene mutations or sporadic late-onset (LOAD) caused various genetic environmental factors. Numerous transgenic rodent models have been developed to understand pathology development progression. The TgF344-AD rat model double that carries two human mutations: APP the Swedish mutation PSEN-1 Δ exon 9 mutations. This exhibits complete repertoire in an age-dependent manner. review summarizes multidisciplinary research insights gained from studying rats context pathology. We explore neuropathological findings; electrophysiological assessments revealing disrupted synaptic transmission, reduced spatial coding, network-level dysfunctions, altered sleep architecture; behavioral studies highlighting impaired memory; alterations excitatory-inhibitory systems; molecular physiological changes emphasizing their age-related effects. Additionally, impact interventions studied compiled, underscoring role bridging gaps understanding pathogenesis. offers significant potential identifying biomarkers for early detection therapeutic interventions, providing robust platform advancing translational research.

Язык: Английский

Процитировано

0