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

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(11), P. 5954 - 5954

Published: May 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.

Language: Английский

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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

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Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 23, 2024

Abstract Alzheimer’s disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate diverse, stemming from a combination factors such aging, genetics, environment. Our current understanding AD pathologies involves various hypotheses, cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, abnormal autophagy. Nonetheless, unraveling interplay among these pathological aspects pinpointing primary initiators require further elucidation validation. In past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available primarily offer symptomatic relief often accompanied by undesirable side However, recent approvals aducanumab ( 1 ) lecanemab 2 Food Drug Administration (FDA) present potential in disrease-modifying Nevertheless, long-term efficacy safety need Consequently, quest for safer more effective persists formidable pressing task. This review discusses pathogenesis, advances diagnostic biomarkers, latest updates trials, emerging technologies drug development. We highlight progress discovery selective inhibitors, dual-target allosteric modulators, covalent proteolysis-targeting chimeras (PROTACs), protein-protein interaction (PPI) modulators. goal provide insights into prospective development application novel drugs.

Language: Английский

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Dietary polyphenols: regulate the advanced glycation end products-RAGE axis and the microbiota-gut-brain axis to prevent neurodegenerative diseases

Critical Reviews in Food Science and Nutrition, Journal Year: 2022, Volume and Issue: 63(29), P. 9816 - 9842

Published: May 19, 2022

Advanced glycation end products (AGEs) are formed in non-enzymatic reaction, oxidation, rearrangement and cross-linking between the active carbonyl groups of reducing sugars free amines amino acids. The Maillard reaction is related to sensory characteristics thermal processed food, while AGEs food matrix this process. a key link stress neurodegenerative disease. can interact with receptors for (RAGE), causing oxidative stress, inflammation response signal pathways activation diseases. Neurodegenerative diseases closely gut microbiota imbalance intestinal inflammation. Polyphenols multiple hydroxyl showed powerful ability scavenge ROS capture α-dicarbonyl species, which led formation mono- di- adducts, thereby inhibiting formation. be effectively prevented by production, interaction RAGEs, or regulating microbiota-gut-brain axis. These strategies include polyphenols multifunctional effects on inhibition, RAGE-ligand interactions blocking, abundance diversity microbiota, alleviation delay prevent progress. It wise promising strategy supplement dietary preventing via AGEs-RAGE axis regulation.

Language: Английский

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

Frontiers in Synaptic Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: March 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.

Language: Английский

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Sleep disorders cause Parkinson's disease or the reverse is true: Good GABA good night

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(3)

Published: March 1, 2024

Parkinson's disease (PD) is a progressive neurodegenerative brain due to degeneration of dopaminergic neurons (DNs) presented with motor and non-motor symptoms. PD symptoms are developed in response the disturbance diverse neurotransmitters including γ-aminobutyric acid (GABA). GABA has neuroprotective effect against neuropathology by protecting DNs substantia nigra pars compacta (SNpc). It been shown that GABAergic linked progression neurotransmission necessary pathway for normal sleep patterns, thus deregulation could be potential cause disorders PD.

Language: Английский

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The Role of the GABAergic System in Diseases of the Central Nervous System

Neuroscience, Journal Year: 2021, Volume and Issue: 470, P. 88 - 99

Published: July 6, 2021

Language: Английский

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The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer’s disease

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 17, 2022

Since type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer’s disease (AD) and both have the same pathogenesis (e.g., insulin resistance), drugs used to treat T2DM been gradually found reduce progression of AD in models. Of these drugs, glucagon-like peptide 1 receptor (GLP-1R) agonists are more effective fewer side effects. GLP-1R reducing neuroinflammation oxidative stress, neurotrophic effects, decreasing Aβ deposition tau hyperphosphorylation models, which may be potential drug treatment AD. However, this needs verified by further clinical trials. This study aims summarize current information on mechanisms effects

Language: Английский

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The landscape of metabolic brain alterations in Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2022, Volume and Issue: 19(3), P. 980 - 998

Published: July 13, 2022

Alzheimer's disease (AD) is accompanied by metabolic alterations both in the periphery and central nervous system. However, so far, a global view of AD-associated changes brain has been missing.

Language: Английский

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The Yin and Yang of GABAergic and Glutamatergic Synaptic Plasticity: Opposites in Balance by Crosstalking Mechanisms

Frontiers in Synaptic Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: May 19, 2022

Synaptic plasticity is a critical process that regulates neuronal activity by allowing neurons to adjust their synaptic strength in response changes activity. Despite the high proximity of excitatory glutamatergic and inhibitory GABAergic postsynaptic zones functional integration within dendritic regions, concurrent has historically been underassessed. Growing evidence for pathological disruptions excitation inhibition (E/I) balance neurological neurodevelopmental disorders indicates need an improved, more "holistic" understanding interplay. There continues be long-standing focus on persistent strengthening (excitatory long-term potentiation; eLTP) its role learning memory, although importance potentiation (iLTP) depression (iLTD) become increasingly apparent. Emerging further points dynamic dialogue between synapses, but much remains understood regarding mechanisms extent this exchange. In mini-review, we explore calcium signaling crosstalk play regulating excitability. We examine current knowledge synapse responses perturbances activity, with induced short-term pharmacological treatments which act either enhance or reduce excitability via ionotropic receptor regulation culture. To delve deeper into potential crosstalk, discuss influence key regulatory proteins, including kinases, phosphatases, structural/scaffolding proteins. Finally, briefly suggest avenues future research better understand synapses.

Language: Английский

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