Expression of Neuronal Nicotinic Acetylcholine Receptor and Early Oxidative DNA Damage in Aging Rat Brain—The Effects of Memantine DOI Open Access
Małgorzata Lewandowska, Agata Różycka, Teresa Grzelak

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1634 - 1634

Опубликована: Фев. 14, 2025

Aging and age-related neurodegenerative disorders are characterized by the dysfunction or loss of brain nicotinic acetylcholine receptors (nAChRs), these changes may be related to other senescence markers, such as oxidative stress DNA repair dysfunction. However, mechanism nAChR in aging modification this process drugs (e.g., memantine, Mem) not yet fully understood. To study whether differences expression rat occur due modulated Mem, we analyzed subunits (at RNA protein levels) biomarkers real-time quantitative polymerase chain reaction (RQ-PCR) Western blot validation. Twenty-one female Wistar rats were divided into four groups, depending on age, oldest group received injections Mem water with use intragastric catheters. We studied cerebral grey matter (CGM), subcortical white (SCWM), cerebellum (Ce). Results showed an decrease α7 mRNA level SCWM. The was accompanied reduced 8-oxoguanine glycosylase 1 (OGG1) increased tumor necrosis factor alpha (TNFα) level. In group, observed a higher SCWM Ce. Biomarker levels changed, but different extent area. Importantly, antioxidative status stopped even regressed under treatment. After two weeks treatment, increase TP53 8-oxo-2'deoxyguanosine (8-oxo-2'dG) observed. conclude that administration protective against mechanisms.

Язык: Английский

Targeting Cytokine-Mediated Inflammation in Brain Disorders: Developing New Treatment Strategies DOI Creative Commons
Rahul Mallick, Sanjay Basak, Parimal Chowdhury

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(1), С. 104 - 104

Опубликована: Янв. 15, 2025

Cytokine-mediated inflammation is increasingly recognized for playing a vital role in the pathophysiology of wide range brain disorders, including neurodegenerative, psychiatric, and neurodevelopmental problems. Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) cause neuroinflammation, alter function, accelerate disease development. Despite progress understanding these pathways, effective medicines targeting are still limited. Traditional anti-inflammatory immunomodulatory drugs peripheral inflammatory illnesses. Still, they face substantial hurdles when applied to central nervous system (CNS), blood-brain barrier (BBB) unwanted systemic effects. This review highlights developing treatment techniques modifying cytokine-driven focusing on advances that selectively target critical involved pathology. Novel approaches, cytokine-specific inhibitors, antibody-based therapeutics, gene- RNA-based interventions, sophisticated drug delivery systems like nanoparticles, show promise with respect lowering neuroinflammation greater specificity safety. Furthermore, developments biomarker discoveries neuroimaging improving our ability monitor responses, allowing more accurate personalized regimens. Preclinical clinical trial data demonstrate therapeutic potential tailored techniques. However, significant challenges remain, across BBB reducing off-target As research advances, creation personalized, cytokine-centered therapeutics has therapy landscape illnesses, giving patients hope better results higher quality life.

Язык: Английский

Процитировано

1

Alzheimer’s Disease: Exploring the Landscape of Cognitive Decline DOI Creative Commons

Rumiana Tenchov,

Janet M. Sasso, Qiongqiong Angela Zhou

и другие.

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(21), С. 3800 - 3827

Опубликована: Окт. 11, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. The pathology of AD marked the accumulation amyloid beta plaques tau protein tangles in brain, along with neuroinflammation synaptic dysfunction. Genetic factors, such as mutations APP, PSEN1, PSEN2 genes, well APOE ε4 allele, contribute to increased risk acquiring AD. Currently available treatments provide symptomatic relief but do not halt progression. Research efforts are focused on developing disease-modifying therapies that target underlying pathological mechanisms Advances identification validation reliable biomarkers for hold great promise enhancing early diagnosis, monitoring progression, assessing treatment response clinical practice effort alleviate burden this devastating disease. In paper, we analyze data from CAS Content Collection summarize research progress We examine publication landscape insights into current knowledge advances developments. also review most discussed emerging concepts assess strategies combat explore genetic pharmacological targets, comorbid diseases. Finally, inspect applications products against their development pipelines drug repurposing. objective broad overview evolving regarding AD, outline challenges, evaluate growth opportunities further combating

Язык: Английский

Процитировано

6

Deciphering the Functions of Raphe–Hippocampal Serotonergic and Glutamatergic Circuits and their Deficits in Alzheimer’s Disease DOI Open Access
Wanting Yu, R Zhang,

Aosheng Zhang

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1234 - 1234

Опубликована: Янв. 30, 2025

Subcortical innervation of the hippocampus by raphe nucleus is essential for emotional and cognitive control. The two major afferents from to originate serotonergic glutamatergic neurons, which control hippocampal inhibitory network, theta activity, synaptic plasticity have been extensively explored in growing body literature, whereas those circuits received little attention. Notably, both between are disrupted Alzheimer's disease (AD), may contribute initiation progression behavioral psychological symptoms dementia. Thus, deciphering mechanism underlying abnormal raphe-hippocampal AD crucial prevent dementia-associated symptoms. In this review, we summarize anatomical, neurochemical, electrophysiological diversity nuclei as well architecture circuitry. We then elucidate subcortical activity their role regulation emotion cognition. Additionally, present an overview pathogenesis analyze available therapies that can potentially be used clinically alleviate neuropsychiatric decline course.

Язык: Английский

Процитировано

0

Expression of Neuronal Nicotinic Acetylcholine Receptor and Early Oxidative DNA Damage in Aging Rat Brain—The Effects of Memantine DOI Open Access
Małgorzata Lewandowska, Agata Różycka, Teresa Grzelak

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1634 - 1634

Опубликована: Фев. 14, 2025

Aging and age-related neurodegenerative disorders are characterized by the dysfunction or loss of brain nicotinic acetylcholine receptors (nAChRs), these changes may be related to other senescence markers, such as oxidative stress DNA repair dysfunction. However, mechanism nAChR in aging modification this process drugs (e.g., memantine, Mem) not yet fully understood. To study whether differences expression rat occur due modulated Mem, we analyzed subunits (at RNA protein levels) biomarkers real-time quantitative polymerase chain reaction (RQ-PCR) Western blot validation. Twenty-one female Wistar rats were divided into four groups, depending on age, oldest group received injections Mem water with use intragastric catheters. We studied cerebral grey matter (CGM), subcortical white (SCWM), cerebellum (Ce). Results showed an decrease α7 mRNA level SCWM. The was accompanied reduced 8-oxoguanine glycosylase 1 (OGG1) increased tumor necrosis factor alpha (TNFα) level. In group, observed a higher SCWM Ce. Biomarker levels changed, but different extent area. Importantly, antioxidative status stopped even regressed under treatment. After two weeks treatment, increase TP53 8-oxo-2'deoxyguanosine (8-oxo-2'dG) observed. conclude that administration protective against mechanisms.

Язык: Английский

Процитировано

0