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

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 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.

Язык: Английский

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Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use

Molecules, Год журнала: 2022, Номер 27(17), С. 5481 - 5481

Опубликована: Авг. 26, 2022

Despite advances in antimicrobial and anti-inflammatory therapies, inflammation its consequences still remain a significant problem medicine. Acute inflammatory responses are responsible for directly life-threating conditions such as septic shock; on the other hand, chronic can cause degeneration of body tissues leading to severe impairment their function. Neuroinflammation is defined an response central nervous system involving microglia, astrocytes, cytokines including chemokines. It considered important neurodegerative diseases, Alzheimer's disease, Parkinson's disease amyotrophic lateral sclerosis. Lipopolysaccharide (LPS) strong immunogenic particle present outer membrane Gram-negative bacteria. major triggering factor cascade bacteria infection. The use LPS pro-inflammatory agent well-known model applied both vivo vitro studies. This review offers summary pathogenesis associated with exposure, especially field neuroinflammation. Moreover, we analyzed different models utilized area neuroscience. paper presents recent knowledge focused new insights experimental model.

Язык: Английский

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Apoptosis in Alzheimer’s disease: insight into the signaling pathways and therapeutic avenues

APOPTOSIS, Год журнала: 2023, Номер 28(7-8), С. 943 - 957

Опубликована: Апрель 26, 2023

Язык: Английский

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Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(7), С. 6518 - 6518

Опубликована: Март 30, 2023

Alzheimer’s disease is one of the most commonly diagnosed cases senile dementia in world. It an incurable process, often leading to death. This multifactorial, and factor this inflammation. Numerous mediators secreted by inflammatory cells can cause neuronal degeneration. Neuritis may coexist with other mechanisms disease, contributing progression, also directly underlie AD. Although much has been established about processes pathogenesis AD, many aspects remain unexplained. The work devoted particular pathomechanism inflammation its role diagnosis treatment. An in-depth detailed understanding neuroinflammation help development diagnostic methods for early contribute new therapeutic strategies disease.

Язык: Английский

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Neuroinflammation in Vascular Cognitive Impairment and Dementia: Current Evidence, Advances, and Prospects

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(11), С. 6224 - 6224

Опубликована: Июнь 2, 2022

Vascular cognitive impairment and dementia (VCID) is a major heterogeneous brain disease caused by multiple factors, it the second most common type of in world. It long-term chronic low perfusion whole or local area, eventually develops into severe dysfunction syndrome. Because disease's ambiguous classification diagnostic criteria, there no clear treatment strategy for VCID, association between cerebrovascular pathology controversial. Neuroinflammation an immunological cascade reaction mediated glial cells central nervous system where innate immunity resides. Inflammatory reactions could be triggered various damaging events, including hypoxia, ischemia, infection. Long-term hypoperfusion-induced ischemia hypoxia can overactivate neuroinflammation, causing apoptosis, blood-brain barrier damage other pathological changes, triggering aggravating occurrence development VCID. In this review, we will explore mechanisms neuroinflammation induced hypoperfusion emphasize important role VCID from perspective immune cells, mediators signaling pathways, so as to provide valuable ideas prevention disease.

Язык: Английский

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Gut liver brain axis in diseases: the implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Дек. 6, 2023

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In past few decades, breakthrough progress has been made in gut liver brain axis, mainly through understanding its formation mechanism increasing treatment strategies. this review, we discuss various complex networks including barrier permeability, hormones, microbial metabolites, vagus nerve, neurotransmitters, immunity, toxic β-amyloid (Aβ) metabolism, epigenetic regulation gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet nanotechnology application regulate Besides, some special treatments targeting gut-liver include farnesoid X receptor (FXR) agonists, takeda G protein-coupled 5 (TGR5) glucagon-like peptide-1 (GLP-1) antagonists fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain embraces cognitive behavioral therapy (CBT), antidepressants tryptophan metabolism-related therapies. liver-brain contains Aβ future, better interactions will promote development novel preventative strategies discovery precise therapeutic targets multiple diseases.

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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Oxidative stress in Alzheimer’s disease: current knowledge of signaling pathways and therapeutics

Molecular Biology Reports, Год журнала: 2024, Номер 51(1)

Опубликована: Янв. 2, 2024

Язык: Английский

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Immunopharmacological Activities of Luteolin in Chronic Diseases

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2136 - 2136

Опубликована: Янв. 21, 2023

Flavonoids have been shown to anti-oxidative effects, as well other health benefits (e.g., anti-inflammatory and anti-tumor functions). Luteolin (3′, 4′, 5,7-tetrahydroxyflavone) is a flavonoid found in vegetables, fruits, flowers, herbs, including celery, broccoli, green pepper, navel oranges, dandelion, peppermint, rosemary. has multiple useful especially regulating inflammation-related symptoms diseases. In this paper, we summarize the studies about immunopharmacological activity of luteolin on anti-inflammatory, anti-cardiovascular, anti-cancerous, anti-neurodegenerative diseases published since 2018 available PubMed or Google Scholar. review, also introduce some additional formulations improve its solubility bioavailability.

Язык: Английский

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Nitric Oxide/Nitric Oxide Synthase System in the Pathogenesis of Neurodegenerative Disorders—An Overview

Antioxidants, Год журнала: 2023, Номер 12(3), С. 753 - 753

Опубликована: Март 20, 2023

Nitric oxide, a ubiquitous molecule found throughout the natural world, is key implicated in many central and benefic molecular pathways has well-established role function of nervous system, as numerous studies have previously shown. Dysregulation its metabolism, mainly upregulation nitric oxide production, been proposed trigger and/or aggravator for neurological affections. Increasing evidence supports implication this prevalent neurodegenerative diseases, such Parkinson’s disease, Alzheimer’s or amyotrophic lateral sclerosis. The mechanisms neurotoxicity center around increased quantities that are produced brain, their cause, and, most importantly, pathological metabolic cascades created. These lead to formation neuronal toxic substances impair neurons’ structure on multiple levels. purpose review present main causes well important pathophysiological triggered by could help explain part complex picture diseases develop targeted therapies.

Язык: Английский

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