Combined Experimental and Computational Investigations of 4‐Amino‐2‐Chloro‐6,7‐Dimethoxyquinazoline as Potential Anti‐Alzheimer Agent DOI

Karthikeyan Asokan,

Karthik Nallasamy,

S. Sivaraman

и другие.

International Journal of Quantum Chemistry, Год журнала: 2024, Номер 124(24)

Опубликована: Дек. 10, 2024

ABSTRACT Alzheimer's disease (AD) is a neurodegenerative condition that leads to the deterioration of brain cells, resulting in memory loss, thinking, and executive skills. In this work, 4‐amino‐2‐chloro‐6,7‐dimethoxyquinazoline (ACDQ) has been studied using 6–311++G(d,p) B3LYP functional density theory (DFT) approach utilizing basis set. Geometry optimization fundamental vibrational frequencies are calculated above method. The spectroscopic investigations such as FT‐IR, FT‐Raman, UV–Vis spectra performed on selected compound. time‐dependent DFT calculations gas water phases determine electronic properties energy gap same Charge distributions have used illustrate between highest occupied lowest unoccupied molecular orbitals. Mulliken population analysis atomic charges ACDQ. From natural bond orbital analysis, it observed there significant electron delocalization ACDQ due presence intramolecular interactions. To evaluate ACDQ's anti‐Alzheimer potential, docking simulation assess its structural stability biological activity against proteins associated with disease. Our study revealed that, strong interaction 4EY7 protein binding −8.1 kcal mol −1 . Additionally, metrics root mean square deviation (RMSD), fluctuation (RMSF), radius gyration considered ( R g ) were computed dynamics simulations protein–ligand interaction. Studies ADMET prediction also carried out. findings current support potential an effective lead therapeutic for

Язык: Английский

Blood-based biomarkers in mild behavioral impairment: an updated overview DOI Creative Commons
Efthalia Angelopoulou,

Xenia Androni,

Chiara Villa

и другие.

Frontiers in Neurology, Год журнала: 2025, Номер 16

Опубликована: Фев. 6, 2025

Identifying individuals at-risk for dementia is one of the critical objectives current research efforts, highlighting need simple, cost-effective, and minimally invasive biomarkers. Mild behavioral impairment (MBI), characterized by emergence persistent neuropsychiatric manifestations in older adults, has attracted increasing attention as a potential early indicator cognitive decline dementia. A growing number studies have recently begun to explore relationship between MBI several blood-based biomarkers associated with Alzheimer's disease (AD) pathology, neurodegeneration, well systemic metabolic inflammatory dysregulation. In this context, been lower plasma Aβ42/Αβ40 ratio, higher phosphorylated tau at threonine 181 (p-tau181), increased neurofilament light chain (NfL) levels, disturbances markers, including homocysteine, insulin ferritin, suggesting multifaceted neurobiological basis syndrome. These findings offer insights into underlying pathophysiology MBI, connection symptoms progression AD. narrative review, we aim summarize critically discuss emerging literature evidence linking biomarkers, hoping shed more on MBI's pathophysiology, its AD-related neurobiology, practical utility predicting impairment, guiding interventions managing risk

Язык: Английский

Процитировано

0

The prevalence of mild behavioral impairment in older adults with mild cognitive impairment: A systematic review and meta-analysis DOI Creative Commons
Yan Zhao, Chang Tan, Yingjing Lu

и другие.

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

Опубликована: Март 28, 2025

Background Mild behavioral impairment is a neurobehavioral symptom characterized by the onset of new and persistent neuropsychiatric syndrome. Patients with co-occurring mild cognitive have relatively highest probability developing dementia than sick or alone. Objective This study aimed to determine currently available best estimate prevalence clarify reasons for difference in estimates. Methods Data were retrieved collected from five electronic databases. Two reviewers independently appraised methodological quality included studies. Heterogeneity was assessed using I² statistic random effects models employed. Sources heterogeneity investigated subgroup analysis meta-regression. All statistical analyses conducted Stata. Results A total 23 reports involving 5397 participants this systematic review. The pooled effect size overall 52% (95%CI 42-62%). In regression analysis, we found that type, area, assessment tools, subject gender could explain part source heterogeneity. Conclusions results review suggest combined impairment; there close relationship between two. Future studies should pay more attention underlying mechanism two provide scientific basis early discrimination clinical Alzheimer's disease.

Язык: Английский

Процитировано

0

Unraveling the Potential Underlying Mechanisms of Mild Behavioral Impairment: Focusing on Amyloid and Tau Pathology DOI Creative Commons
Efthalia Angelopoulou, Anastasia Bougea, Alexandros Hatzimanolis

и другие.

Cells, Год журнала: 2024, Номер 13(13), С. 1164 - 1164

Опубликована: Июль 8, 2024

The emergence of sustained neuropsychiatric symptoms (NPS) among non-demented individuals in later life, defined as mild behavioral impairment (MBI), is linked to a higher risk cognitive decline. However, the underlying pathophysiological mechanisms remain largely unexplored. A growing body evidence has shown that MBI associated with alterations structural and functional neuroimaging studies, genetic predisposition clinical diagnosis Alzheimer’s disease (AD), well amyloid tau pathology assessed blood, cerebrospinal fluid, positron-emission tomography (PET) imaging neuropathological examination. These findings shed more light on MBI-related potential neurobiological mechanisms, paving way for development targeted pharmacological approaches. In this review, we aim discuss available role mechanisms. Dysregulation hypothalamic–pituitary–adrenal (HPA) axis, disruption neurotrophic factors, such brain-derived factor (BDNF), abnormal neuroinflammatory responses including kynurenine pathway, dysregulation transforming growth beta (TGF-β1), epigenetic micro-RNA (miR)-451a miR-455-3p, synaptic dysfunction, imbalance neurotransmitters acetylcholine, dopamine, serotonin, gamma-aminobutyric acid (GABA) norepinephrine, altered locus coeruleus (LC) integrity are some connecting pathology. elucidation neurobiology would facilitate design efficacy relative trials, especially towards amyloid- or tau-related pathways. addition, provide insights future research into our deeper understanding its pathophysiology MBI, therapeutic implications.

Язык: Английский

Процитировано

2

Human Leukocyte Antigen and microRNAs as Key Orchestrators of Mild Cognitive Impairment and Alzheimer’s Disease: A Systematic Review DOI Open Access
Cristina-Sorina Cătană, Monica Mihaela Marta, Mădălina Văleanu

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8544 - 8544

Опубликована: Авг. 5, 2024

The expression of inflamma-miRs and human leukocyte antigen (HLA) haplotypes could indicate mild cognitive impairment (MCI) Alzheimer’s disease (AD). We used international databases to conduct a systematic review studies on HLA variants meta-analysis research microRNAs (miRNAs). aimed analyze the discriminative value miRNAs in MCI, AD controls evaluate protective or causative effect decline, establish role as biomarkers for early detection AD, find possible link between HLA. Statistical analysis was conducted using Comprehensive Meta-analysis software, version 2.2.050 (Biostat Inc., Englewood, NJ, USA). sizes were estimated by logarithm base 2 fold change. revealed that some variants, such HLA-B*4402, HLA-A*33:01, HLA-DPB1, HLA-DR15, HLA-DQB1*03:03, HLA-DQB1*06:01, HLA-DQB1*03:01, SNPs HLA-DRB1/DQB1, HLA-DQA1, predisposed decline before occurrence while HLA-A1*01, HLA-DRB1∗13:02, HLA-DRB1*04:04, HLA-DRB1*04:01 demonstrated role. identified let-7 miR-15/16 AD. association these two miRNA families predispose be screening prevention MCI.

Язык: Английский

Процитировано

1

Pathophysiology of Alzheimer’s disease: an insight into the genetic factors, hypotheses, redox imbalance, and antioxidant intervention DOI
Teslim Simisola Abdulkadir, Joseph Olusegun Ayo

Comparative Clinical Pathology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 13, 2024

Язык: Английский

Процитировано

1

Neobavaisoflavone Ameliorates Memory Deficits and Brain Damage in Aβ25‐35‐Induced Mice by Regulating SIRT1 DOI Creative Commons

Fengxiao Hao,

Mengnan Zeng, Bing Cao

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(10)

Опубликована: Окт. 1, 2024

ABSTRACT Background Alzheimer's disease (AD) is a common chronic neurodegenerative in older people, and there no specific treatment that can stop or reverse its progression. Neobavaisoflavone (NBIF) flavonoid has been shown to have neuroprotective effects, but role AD not revealed. The present study investigated the mechanism of NBIF on Aβ 25‐35 ‐induced brain injury. Methods In this experiment, mouse model was established by injection peptides (200 μM, icv), Donepezil (Don, 10 mg/kg/days), NBIF‐L (15 NBIF‐H (30 mg/kg/days) were administered orally for 4 weeks. Learning memory, hippocampal pathological changes, markers, apoptosis, oxidative stress, inflammation, immune cells measured mice. Network pharmacology combined with GEO database led identification SIRT1, key target intervention AD, levels p‐STAT3 FOXO1 measured. addition, antagonistic activity SIRT1 transfection silencing against N9 N2a‐APP69 assess whether effects caused mediated SIRT1. Results results showed ameliorated learning memory neuronal damage, reduced stress neuroinflammation, modulated cells. upregulates reduces expression FOXO1. Furthermore, effectively protective effect cells, which indicated related Conclusions injury inhibiting may be through signaling. These findings provide rationale help facilitate development clinical therapeutic agents AD.

Язык: Английский

Процитировано

1

Apolipoprotein E (APOE) Isoforms, Neuropsychiatric Symptoms, and Sporadic Alzheimer’s Disease DOI

Giuseppe Berardino,

Anita Mollica,

Antonello Bellomo

и другие.

Springer eBooks, Год журнала: 2024, Номер unknown, С. 1 - 17

Опубликована: Янв. 1, 2024

Язык: Английский

Процитировано

0

Mild behavioral impairment in people with mild cognitive impairment: Are the two conditions related? DOI
Julia-Sophia Scheuermann, Elmar Graessel, André Kratzer

и другие.

Journal of Alzheimer s Disease, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 8, 2024

Mild cognitive impairment (MCI) and mild behavioral (MBI) are both considered potential prodromal stages of dementia, especially Alzheimer's disease. Previous literature has lacked specific information about MBI in individuals with MCI associations several aspects both, MCI.

Язык: Английский

Процитировано

0

Combined Experimental and Computational Investigations of 4‐Amino‐2‐Chloro‐6,7‐Dimethoxyquinazoline as Potential Anti‐Alzheimer Agent DOI

Karthikeyan Asokan,

Karthik Nallasamy,

S. Sivaraman

и другие.

International Journal of Quantum Chemistry, Год журнала: 2024, Номер 124(24)

Опубликована: Дек. 10, 2024

ABSTRACT Alzheimer's disease (AD) is a neurodegenerative condition that leads to the deterioration of brain cells, resulting in memory loss, thinking, and executive skills. In this work, 4‐amino‐2‐chloro‐6,7‐dimethoxyquinazoline (ACDQ) has been studied using 6–311++G(d,p) B3LYP functional density theory (DFT) approach utilizing basis set. Geometry optimization fundamental vibrational frequencies are calculated above method. The spectroscopic investigations such as FT‐IR, FT‐Raman, UV–Vis spectra performed on selected compound. time‐dependent DFT calculations gas water phases determine electronic properties energy gap same Charge distributions have used illustrate between highest occupied lowest unoccupied molecular orbitals. Mulliken population analysis atomic charges ACDQ. From natural bond orbital analysis, it observed there significant electron delocalization ACDQ due presence intramolecular interactions. To evaluate ACDQ's anti‐Alzheimer potential, docking simulation assess its structural stability biological activity against proteins associated with disease. Our study revealed that, strong interaction 4EY7 protein binding −8.1 kcal mol −1 . Additionally, metrics root mean square deviation (RMSD), fluctuation (RMSF), radius gyration considered ( R g ) were computed dynamics simulations protein–ligand interaction. Studies ADMET prediction also carried out. findings current support potential an effective lead therapeutic for

Язык: Английский

Процитировано

0