An Expanded Narrative Review of Neurotransmitters on Alzheimer’s Disease: The Role of Therapeutic Interventions on Neurotransmission

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disease. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles are the key players responsible for pathogenesis Aβ affect balance in chemical neurotransmitters brain. Thus, current review examined role discusses alterations neurochemical activity cross talk with their receptors transporters. In presence tangles, changes may occur expression neuronal which turn triggers excessive release glutamate into synaptic cleft contributing to cell death damage. GABAergic system also be affected by AD pathology similar way. addition, decreased cholinergic dysfunction dopamine neurotransmission contribute damage cognitive function. Moreover, deficiencies noradrenergic neurons within locus coeruleus suggests that stimulation could useful addressing its pathophysiology. regulation melatonin, known effectiveness enhancing function preventing accumulation, along involvement serotonergic histaminergic cognition memory, becomes remarkable promoting AD. Additionally, nitric oxide adenosine-based therapeutic approaches play protective neuroinflammation. Overall, neurotransmitter-based strategies emerge as pivotal neurotransmitter homeostasis context This discussed potential drugs effective slowing correcting processes targeting imbalance Therefore, serve future strategy tackle

Language: Английский

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Comprehensive Review of Nutraceuticals against Cognitive Decline Associated with Alzheimer’s Disease

ACS Omega, Journal Year: 2023, Volume and Issue: 8(39), P. 35499 - 35522

Published: Sept. 20, 2023

Nowadays, nutraceuticals are being incorporated into functional foods or used as supplements with nonpharmacological approaches in the prevention and management of several illnesses, including age-related conditions chronic neurodegenerative diseases. Nutraceuticals apt for preventing treating such disorders because their nontoxic, non-habit-forming, efficient bioactivities promoting neurological well-being due to ability influence cellular processes neurogenesis, synaptogenesis, synaptic transmission, neuro-inflammation, oxidative stress, cell death modulation, neuronal survival. The capacity modify all these reveals potential develop food-based strategies aid brain development enhance function, prevent ameliorate neurodegeneration, possibly reverse cognitive impairment observed Alzheimer's disease, most predominant form dementia elderly. current review summarizes experimental evidence neuroprotective against describing mechanisms action vitro vivo models applied evaluate potential.

Language: Английский

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Targeting galectin-3 to counteract spike-phase uncoupling of fast-spiking interneurons to gamma oscillations in Alzheimer’s disease

Translational Neurodegeneration, Journal Year: 2023, Volume and Issue: 12(1)

Published: Feb. 6, 2023

Alzheimer's disease (AD) is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment exists. Neuroinflammation central to the pathology progression, with evidence suggesting that microglia-released galectin-3 (gal3) plays pivotal role by amplifying neuroinflammation in AD. However, possible involvement of gal3 disruption neuronal network oscillations typical AD remains unknown.Here, we investigated functional implications signaling on experimentally induced gamma ex vivo (20-80 Hz) performing electrophysiological recordings hippocampal CA3 area wild-type (WT) mice and 5×FAD mouse model In addition, recorded slices from WT under acute application were analyzed RT-qPCR detect expression some neuroinflammation-related genes, amyloid-β (Aβ) plaque load was quantified immunostaining 6-month-old or without Gal3 knockout (KO).Gal3 decreased oscillation power rhythmicity an activity-dependent manner, accompanied impairment cellular dynamics fast-spiking interneurons (FSNs) pyramidal cells. We found gal3-induced mediated carbohydrate-recognition domain prevented inhibitor TD139, also Aβ42-induced degradation oscillations. Furthermore, lacking (5×FAD-Gal3KO) exhibited WT-like Aβ load.We report first time impairs spike-phase uncoupling FSNs, inducing performance collapse. Moreover, our findings suggest inhibition as potential therapeutic strategy counteract instability other neurological disorders encompassing cognitive decline.

Language: Английский

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Amelioration of olfactory dysfunction in a mouse model of Parkinson’s disease via enhancing GABAergic signaling

Cell & Bioscience, Journal Year: 2023, Volume and Issue: 13(1)

Published: June 3, 2023

Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson's disease (PD). As foremost pathological hallmark, α-synuclein initiates pathology in olfactory pathway at early stage PD, particularly epithelium (OE) and bulb (OB). However, local neural microcircuit mechanisms underlying between OE OB PD remain unknown.We observed that odor detection discrimination were impaired 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed increased accumulated but not OE. Notably, hyperactivity mitral/tufted cells excitation/inhibition imbalance found which attributed to GABAergic transmission aberrant expression GABA transporter 1 vesicular OB. We further showed tiagabine, a potent selective reuptake inhibitor, could reverse function signaling mice.Taken together, our findings demonstrate potential synaptic PD. These results highlight critical role diagnosis provide therapeutic strategy for early-stage

Language: Английский

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Factors affecting the GABAergic synapse function in Alzheimer’s disease: Focus on microRNAs

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 92, P. 102123 - 102123

Published: Nov. 13, 2023

Alzheimer's disease (AD) is a progressive neurological characterized by the loss of cognitive function, confusion, and memory deficit. Accumulation abnormal proteins, amyloid beta (Aß), phosphorylated Tau (p-tau) forms plaques tangles that deteriorate synapse resulting in neurodegeneration decline AD. The human brain composed different types neurons and/or synapses are functionally defective GABAergic synapse, most abundant inhibitory neuron was found to be dysfunctional AD contributes disrupting function. This study explored GABA receptors associated with dysfunction various biological environmental factors cause AD, such as Aβ, p-tau, aging, sex, astrocytes, microglia, APOE, mental disorder, diet, physical activity, sleep. Furthermore, we role microRNAs (miRNAs) regulation function disorders states. We also discuss molecular mechanisms underlying focus on miR-27b, miR-30a, miR-190a/b, miR-33, miR-51, miR-129-5p, miR-376-3p, miR-376c, miR-30b miR-502-3p. purpose our article highlight recent research miRNAs affecting contribute progression

Language: Английский

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