Neurotransmitters—Key Factors in Neurological and Neurodegenerative Disorders of the Central Nervous System

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(11), С. 5954 - 5954

Опубликована: Май 25, 2022

Neurotransmitters are molecules that amplify, transmit, and convert signals in cells, having an essential role information transmission throughout the nervous system. Hundreds of such chemicals have been discovered last century, continuing to be identified studied concerning their action on brain health. These substances observed influence numerous functions, including emotions, thoughts, memories, learning, movements. Thus, disturbances neurotransmitters' homeostasis started being correlated with a plethora neurological neurodegenerative disorders. In this respect, present paper aims describe most important neurotransmitters, broadly classified into canonical (e.g., amino acids, monoamines, acetylcholine, purines, soluble gases, neuropeptides) noncanonical neurotransmitters exosomes, steroids, D-aspartic acid), explain link some relevant conditions. Moreover, brief overview recently developed detection methods is offered, followed by several considerations modulation these towards restoring homeostasis.

Язык: Английский

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Therapeutic Effects of Green Tea Polyphenol (‒)-Epigallocatechin-3-Gallate (EGCG) in Relation to Molecular Pathways Controlling Inflammation, Oxidative Stress, and Apoptosis

International Journal of Molecular Sciences, Год журнала: 2022, Номер 24(1), С. 340 - 340

Опубликована: Дек. 25, 2022

(‒)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea. Thanks to multiple interactions with cell surface receptors, intracellular signaling pathways, and nuclear transcription factors, EGCG possesses a wide variety of anti-inflammatory, antioxidant, antifibrotic, anti-remodelation, tissue-protective properties which may be useful treatment various diseases, particularly cancer, neurological, cardiovascular, respiratory, metabolic disorders. This article reviews current information on biological effects above-mentioned disorders relation molecular pathways controlling inflammation, oxidative stress, apoptosis.

Язык: Английский

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New insight into neurological degeneration: Inflammatory cytokines and blood–brain barrier

Frontiers in Molecular Neuroscience, Год журнала: 2022, Номер 15

Опубликована: Окт. 24, 2022

Neurological degeneration after neuroinflammation, such as that resulting from Alzheimer’s disease (AD), stroke, multiple sclerosis (MS), and post-traumatic brain injury (TBI), is typically associated with high mortality morbidity permanent cognitive dysfunction, which places a heavy economic burden on families society. Diagnosing curing these diseases in their early stages remains challenge for clinical investigation treatment. Recent insight into the onset progression of highlights permeability blood–brain barrier (BBB). The primary factor influences BBB structure function inflammation, especially main cytokines including IL-1β, TNFα, IL-6, mechanism disruption are critical component aforementioned diseases. Surprisingly, systematic inflammation can also induce much worse neurological or injuries do. In this review, we will therefore discuss physiological BBB, recent research about inducing impairment, eventually need to prevent BBB.

Язык: Английский

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Role of Microglia and Astrocytes in Alzheimer’s Disease: From Neuroinflammation to Ca2+ Homeostasis Dysregulation

Cells, Год журнала: 2022, Номер 11(17), С. 2728 - 2728

Опубликована: Сен. 1, 2022

Alzheimer’s disease (AD) is the most common form of dementia worldwide, with a complex, poorly understood pathogenesis. Cerebral atrophy, amyloid-β (Aβ) plaques, and neurofibrillary tangles represent main pathological hallmarks AD brain. Recently, neuroinflammation has been recognized as prominent feature brain substantial evidence suggests that inflammatory response modulates progression. Additionally, dysregulation calcium (Ca2+) homeostasis represents another early factor involved in pathogenesis, intracellular Ca2+ concentration essential to ensure proper cellular neuronal functions. Although growing supports involvement mechanisms neurodegeneration-related processes, scant data are available on its contribution microglia astrocytes functioning, both health throughout continuum. Nevertheless, AD-related aberrant signalling crucially underpinning neuroinflammatory processes that, turn, impact function. In this light, we attempted provide an overview current understanding interactions between glia cells-mediated responses molecular AD.

Язык: Английский

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Alzheimer’s disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression

Frontiers in Synaptic Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Март 9, 2023

The synapse has consistently been considered a vulnerable and critical target within Alzheimer’s disease, loss is, to date, one of the main biological correlates cognitive decline disease. This occurs prior neuronal with ample evidence that synaptic dysfunction precedes this, in support idea failure is crucial stage disease pathogenesis. two pathological hallmarks abnormal aggregates amyloid or tau proteins, have had demonstrable effects on physiology animal cellular models There also growing these proteins may synergistic effect neurophysiological dysfunction. Here, we review some findings alterations what know from models. First, briefly summarize human suggest synapses are altered, including how this relates network activity. Subsequently, considered, highlighting mouse pathology role play dysfunction, either isolation examining pathologies interact specifically focuses function observed models, typically measured using electrophysiology calcium imaging. Following loss, it would be impossible imagine not alter oscillatory activity brain. Therefore, discusses underpin aberrant patterns seen patients. Finally, an overview key directions considerations field covered. includes current therapeutics targeted at but methods modulate rescue patterns. Other important future avenues note include non-neuronal cell types such as astrocytes microglia, mechanisms independent will certainly continue for foreseeable future.

Язык: Английский

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Oxidized/unmodified-polyethylene microplastics neurotoxicity in mice: Perspective from microbiota-gut-brain axis

Environment International, Год журнала: 2024, Номер 185, С. 108523 - 108523

Опубликована: Март 1, 2024

Microplastics (MPs) are inevitably oxidized in the environment, and their potential toxicity to organisms has attracted wide attention. However, neurotoxicity mechanism of polyethylene (Ox-PE) MPs remain unclear. Herein, we prepared low-density (Ox-LDPE) established a model exposure by continuously orally gavage C57BL/6 J mice with LDPE-MPs/Ox-LDPE-MPs for 28 days or without oral administration Lactobacillus plantarum DP189 galactooligosaccharides (DP189&GOS). The experimental results indicated that LDPE-MPs Ox-LDPE-MPs caused several adverse effects mice, mainly manifested behavioral changes, disruption intestinal blood–brain barrier (BBB), simultaneous oxidative stress, inflammatory reactions, pathological damage brain intestines. Brain transcriptomic analysis revealed cholinergic synaptic signaling pathways, which affect cognitive function, were significantly disrupted after Ox-LDPE-MPs. Real-time quantitative polymerase chain reaction Western Blotting further demonstrated critical genes (Slc5a7, Chat Slc18a3) proteins (Chat pathway down-regulated These alterations lead reduced acetylcholine concentration, causes dysfunction mice. Importantly, DP189&GOS interventions effectively mitigated MPs-induced microbiota alteration, improved BBB integrity, attenuated stress response, also saw rebound release acetylcholine. exert neurotoxic on inducing responses, dysregulation pathways mouse brain. That probiotic supplementation is effective attenuating Overall, this study reveals mechanisms improvement measures, necessary assess risks plastic contaminants human health.

Язык: Английский

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New insights into the role and mechanisms of ginsenoside Rg1 in the management of Alzheimer’s disease

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 152, С. 113207 - 113207

Опубликована: Июнь 3, 2022

Alzheimer's disease (AD) is a common neurodegenerative disorder in the elderly characterized by memory loss and cognitive dysfunction. The pathogenesis of AD complex. One-targeted anti-AD drugs usually fail to delay progression. Traditional Chinese medicine records have documented use roots Panax ginseng (ginseng roots) its prescriptions treat dementia. Ginsenoside Rg1, main ginsenoside component roots, exhibits certain therapeutic effect abovementioned diseases, suggesting potential management AD. Therefore, we combed currently used drugs, reviewed availability, pharmacokinetics, pharmaceutic studies Rg1. This review summarizes effects mechanisms Rg1 deglycosylated derivatives vivo vitro. include improvement Aβ Tau pathologies, regulation synaptic function intestinal microflora, reduction inflammation, oxidative stress, apoptosis. underlying mainly involve PKC, MAPK, PI3K/Akt, CDK5, GSK-3β, BDNF/TrkB, PKA/CREB, FGF2/Akt, p21WAF1/CIP1, NF-κB, NLRP1, TLR3, TLR4 signaling pathways. As on not been systematically reviewed, provided comprehensive shed light future directions utilization as well development drugs.

Язык: Английский

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Iron Metabolism in Aging and Age-Related Diseases

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(7), С. 3612 - 3612

Опубликована: Март 25, 2022

Iron is a trace metal element necessary to maintain life and also involved in variety of biological processes. Aging refers the natural process which physiological functions various systems, organs, tissues decline, affected by genetic environmental factors. Therefore, it imperative investigate relationship between iron metabolism aging-related diseases, including neurodegenerative diseases. During aging, accumulation nonheme destroys stability intracellular environment. The destruction homeostasis can induce cell damage producing hydroxyl free radicals, leading mitochondrial dysfunction, brain even organismal aging. In this review, we have briefly summarized role metabolic body, then discussed recent developments aging age-related finally, explored some chelators as treatment strategies for those disorders. Understanding roles diseases will fill knowledge gap field. This review could provide new insights into research on

Язык: Английский

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Recent advance on carbamate-based cholinesterase inhibitors as potential multifunctional agents against Alzheimer's disease

European Journal of Medicinal Chemistry, Год журнала: 2022, Номер 240, С. 114606 - 114606

Опубликована: Июль 16, 2022

Язык: Английский

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BACE1 Inhibitors for Alzheimer’s Disease: The Past, Present and Any Future?

Molecules, Год журнала: 2022, Номер 27(24), С. 8823 - 8823

Опубликована: Дек. 12, 2022

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and common cause of dementia in elderly. The complexity AD has hindered development either a cure or disease-modifying therapy to halt progression. Numerous hypotheses were presented order explain mechanisms underlying pathogenesis AD. Introduced 1992, “Amyloid Cascade Hypothesis” had huge impact on field inspired rise various drug candidates, especially amyloid-beta (Aβ)-directed drugs; including beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors. Adopted by number pharmaceutical companies, BACE1 inhibitors gained momentum past decade with promising results from experimental early clinical-phase studies. Nevertheless, nearly all failed later phases clinical trials, due safety and/or efficacy issues, others discontinued favor second-generation small-molecule candidates. This paper aims provide comprehensive review ever reach we discuss challenges different perspectives whether are be reconsidered revitalized future.

Язык: Английский

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