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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Exercise Training Improves Memory Performance in Older Adults: A Narrative Review of Evidence and Possible Mechanisms

Frontiers in Human Neuroscience, Journal Year: 2022, Volume and Issue: 15

Published: Jan. 27, 2022

Graphical Abstract Exercise, neurotransmitters, growth factors, myokines, and potential effects on the brain.

Language: Английский

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Microglia-Astrocyte Communication in Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: 95(3), P. 785 - 803

Published: Aug. 25, 2023

Microglia and astrocytes are regarded as active participants in the central nervous system under various neuropathological conditions, including Alzheimer's disease (AD). Both microglia astrocyte activation have been reported to occur with a spatially temporarily distinct pattern. Acting double-edged sword, glia-mediated neuroinflammation may be both detrimental beneficial brain. In variety of neuropathologies, activated before astrocytes, which facilitates activation. Yet reactive can also prevent adjacent addition helping them become activated. Studies describe changes genetic profile well cellular molecular responses these two types glial cells that contribute dysfunctional immune crosstalk AD. this paper, we construct current knowledge microglia-astrocyte communication, highlighting multifaceted functions their role A thorough comprehension communication could hasten creation novel AD treatment approaches.

Language: Английский

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Mesenchymal and Neural Stem Cell-Derived Exosomes in Treating Alzheimer’s Disease

Bioengineering, Journal Year: 2023, Volume and Issue: 10(2), P. 253 - 253

Published: Feb. 15, 2023

As the most common form of dementia and a progressive neurodegenerative disorder, Alzheimer’s disease (AD) affects over 10% world population with age 65 older. The is neuropathologically associated loss neurons synapses in specific brain regions, deposition amyloid plaques neurofibrillary tangles, neuroinflammation, blood–brain barrier (BBB) breakdown, mitochondrial dysfunction, oxidative stress. Despite intensive effort, there still no cure for disorder. Stem cell-derived exosomes hold great promise treating various diseases, including AD, as they contain variety anti-apoptotic, anti-inflammatory, antioxidant components. Moreover, stem also promote neurogenesis angiogenesis can repair damaged BBB. In this review, we will first outline major neuropathological features AD; subsequently, discussion cells, cell-secreted exosomes, exosome isolation methods follow. We then summarize recent data involving use mesenchymal cell- or neural AD. Finally, briefly discuss challenges, perspectives, clinical trials using AD therapy.

Language: Английский

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siRNA drug delivery across the blood–brain barrier in Alzheimer's disease

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 199, P. 114968 - 114968

Published: June 21, 2023

Language: Английский

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Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer’s disease and 5XFAD mice

Brain, Journal Year: 2024, Volume and Issue: 147(6), P. 2169 - 2184

Published: April 25, 2024

Abstract Approximately 22% of Alzheimer’s disease (AD) patients suffer from seizures, and the co-occurrence seizures epileptiform activity exacerbates AD pathology related cognitive deficits, suggesting that may be a targetable component progression. Given alterations in neuronal excitatory:inhibitory (E:I) balance occur epilepsy, we hypothesized decreased markers inhibition relative to those excitation would present patients. We similarly 5XFAD mice, E:I imbalance progress an early stage (prodromal) later symptomatic stages further exacerbated by pentylenetetrazol (PTZ) kindling. Post-mortem temporal cortical tissues with or without seizure history were examined for changes several balance, including levels inhibitory GABAA receptor, sodium potassium chloride cotransporter 1 (NKCC1) 2 (KCC2) excitatory NMDA AMPA type glutamate receptors. performed patch-clamp electrophysiological recordings CA1 neurons hippocampal slices same prodromal mice. next mice at chronic stages, after PTZ control protocols, response mTORC1 inhibitor rapamycin, administered following kindled balance. found comorbid had worsened functional scores receptor subunit expression, as well increased NKCC1/KCC2 ratios, indicative depolarizing GABA responses. Patch clamp showed intrinsic excitability, along GABAergic transmission altered glutamatergic neurotransmission, indicating stages. Furthermore, induction led dysregulation reduction GluA2 receptors calcium permeable Finally, treatment inhibitor, doses have previously shown attenuate seizure-induced amyloid-β could also reverse elevations ratio these Our data demonstrate novel mechanisms interaction between epilepsy indicate targeting potentially US Food Drug Administration-approved mTOR inhibitors, hold therapeutic promise history.

Language: Английский

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The Interplay between Mitochondrial Dysfunction and Ferroptosis during Ischemia-Associated Central Nervous System Diseases

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(10), P. 1367 - 1367

Published: Sept. 25, 2023

Cerebral ischemia, a leading cause of disability and mortality worldwide, triggers cascade molecular cellular pathologies linked to several central nervous system (CNS) disorders. These disorders primarily encompass ischemic stroke, Alzheimer's disease (AD), Parkinson's (PD), epilepsy, other CNS conditions. Despite substantial progress in understanding treating the underlying pathological processes various neurological diseases, there is still notable absence effective therapeutic approaches aimed specifically at mitigating damage caused by these illnesses. Remarkably, ischemia causes severe cells ischemia-associated diseases. initiates oxygen glucose deprivation, which subsequently promotes mitochondrial dysfunction, including permeability transition pore (MPTP) opening, mitophagy excessive fission, triggering forms cell death such as autophagy, apoptosis, well ferroptosis. Ferroptosis, novel type regulated (RCD), characterized iron-dependent accumulation lethal reactive species (ROS) lipid peroxidation. Mitochondrial dysfunction ferroptosis both play critical roles pathogenic progression In recent years, growing evidence has indicated that interplays with aggravate cerebral injury. However, potential connections between have not yet been clarified. Thus, we analyzed mechanism We also discovered GSH depletion GPX4 inactivation lipoxygenase activation calcium influx following injury, resulting MPTP opening dysfunction. Additionally, electron transport an imbalanced fusion-to-fission ratio can lead ROS iron overload, further contribute occurrence This creates vicious cycle continuously worsens this study, our focus on exploring interplay ferroptosis, may offer new insights into for treatment

Language: Английский

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Symptoms and conventional treatments of Alzheimer's disease

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 213 - 234

Published: Jan. 1, 2024

Language: Английский

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Fyn Kinase in Alzheimer’s Disease: Unraveling Molecular Mechanisms and Therapeutic Implications

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

Published: June 18, 2024

Language: Английский

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Basal forebrain cholinergic neurons are vulnerable in a mouse model of Down syndrome and their molecular fingerprint is rescued by maternal choline supplementation

The FASEB Journal, Journal Year: 2023, Volume and Issue: 37(6)

Published: May 16, 2023

Abstract Basal forebrain cholinergic neuron (BFCN) degeneration is a hallmark of Down syndrome (DS) and Alzheimer's disease (AD). Current therapeutics in these disorders have been unsuccessful slowing progression, likely due to poorly understood complex pathological interactions dysregulated pathways. The Ts65Dn trisomic mouse model recapitulates both cognitive morphological deficits DS AD, including BFCN has shown lifelong behavioral changes maternal choline supplementation (MCS). To test the impact MCS on BFCNs, we performed laser capture microdissection individually isolate acetyltransferase‐immunopositive neurons disomic littermates, conjunction with at onset degeneration. We utilized single population RNA sequencing (RNA‐seq) interrogate transcriptomic within medial septal nucleus (MSN) BFCNs. Leveraging multiple bioinformatic analysis programs differentially expressed genes (DEGs) by genotype diet, identified key canonical pathways altered physiological functions MSN which were attenuated offspring, cholinergic, glutamatergic GABAergic linked differential gene expression bioinformatically neurological functions, motor dysfunction/movement disorder, early disease, ataxia impairment via Ingenuity Pathway Analysis. DEGs may underlie aberrant behavior mice, attenuating underlying changes. propose ameliorates septohippocampal circuit mice through normalization principally glutamatergic, signaling pathways, resulting attenuation functions.

Language: Английский

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