The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Март 6, 2023

Neuronal loss is one of the striking causes various central nervous system (CNS) disorders, including major neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic lateral sclerosis (ALS). Although these diseases have different features clinical manifestations, they share some common mechanisms pathology. Progressive regional neurons in patients responsible for motor, memory, cognitive dysfunctions, leading to disabilities death. cell death linked pathways conditions. Protein misfolding aggregation, mitochondrial dysfunction, generation reactive oxygen species (ROS), activation innate immune response are most critical hallmarks diseases. Thus, endoplasmic reticulum (ER) stress, oxidative neuroinflammation pathological factors neuronal Even though exact not fully discovered, notable role mentioned well known. On this basis, researchers been prompted investigate neuroprotective effects targeting underlying determine a promising therapeutic approach treatment. This review provides an overview ER death, mainly discussing or molecules involved factors.

Язык: Английский

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Mechanisms of ferroptosis in Alzheimer's disease and therapeutic effects of natural plant products: A review

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 164, С. 114312 - 114312

Опубликована: Май 19, 2023

Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by massive loss of specific neurons. It is a progressive disabling, severe and fatal complex disease. Due to its pathogenesis limitations clinical treatment strategies, it poses serious medical challenge burden worldwide. The AD not clear, potential biological mechanisms include aggregation soluble amyloid form insoluble plaques, abnormal phosphorylation tau protein formation intracellular neurofibrillary tangles (NFT), neuroinflammation, ferroptosis, oxidative stress metal ion disorders. Among them, ferroptosis newly discovered programmed cell death induced iron-dependent lipid peroxidation reactive oxygen species. Recent studies have shown that closely related AD, but the mechanism remains unclear. may be iron metabolism, amino acid metabolism affecting accumulation ions. Some chelating agents (deferoxamine, deferiprone), chloroiodohydroxyquine derivatives, antioxidants (vitamin E, lipoic acid, selenium), derivatives Fer-1, tet, etc. been in animal effective exert neuroprotective effects. This review summarizes regulation natural plant products on order provide reference information for future research development inhibitors.

Язык: Английский

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Alzheimer's disease pathophysiology in the Retina

Progress in Retinal and Eye Research, Год журнала: 2024, Номер 101, С. 101273 - 101273

Опубликована: Май 15, 2024

The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks AD, including amyloid β-protein (Aβ) deposits abnormal tau protein isoforms, in retinas AD patients animal models. Moreover, structural functional vascular abnormalities such as reduced blood flow, Aβ deposition, blood-retinal barrier damage, along with inflammation neurodegeneration, been described mild cognitive impairment dementia. Histological, biochemical, clinical studies demonstrated that nature severity pathologies brain correspond. Proteomics analysis revealed a similar pattern dysregulated proteins biological pathways patients, enhanced inflammatory neurodegenerative processes, impaired oxidative-phosphorylation, mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific deposits, well vasculopathy neurodegeneration living suggesting alterations at different stages links to pathology. Current exploratory ophthalmic modalities, optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, hyperspectral imaging, may offer promise assessment AD. However, further research needed deepen our understanding AD's impact on its progression. To advance this field, future require replication larger diverse cohorts confirmed biomarkers standardized retinal techniques. This will validate aiding early screening monitoring.

Язык: Английский

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Tracking neuroinflammatory biomarkers in Alzheimer’s disease: a strategy for individualized therapeutic approaches?

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Июль 30, 2024

Abstract Background Recent trials of anti-amyloid-β (Aβ) monoclonal antibodies, including lecanemab and donanemab, in early Alzheimer disease (AD) showed that these drugs have limited clinical benefits their use comes with a significant risk serious adverse events. Thus, it seems crucial to explore complementary therapeutic approaches. Genome-wide association studies identified robust associations between AD several genes related immune response, but not restricted CD33 TREM2 . Here, we critically reviewed the current knowledge on candidate neuroinflammatory biomarkers role characterizing pathophysiology AD. Main body Neuroinflammation is recognized be contributing component pathogenesis. The fact neuroinflammation most likely present from earliest pre-stages co-occurs deposition Aβ reinforces need precisely define sequence nature Numerous involving anti-inflammatory previously yielded unfavorable outcomes mild-to-moderate Although reasons behind failures remain unclear, may include time target selected for intervention. Indeed, our review, observed stage-dependent process brain. While initial activation glial cells counteracts brain deposition, downregulation functional state microglia occurs at more advanced stages. To address this issue, personalized modulation therapy required. emergence reliable blood-based biomarkers, particularly fibrillary acidic protein, marker reactive astrocytes, facilitate classification patients based ATI(N) biomarker framework. This expands upon traditional (“A”), tau (“T”), neurodegeneration (“N”), by incorporating novel inflammatory (“I”). Conclusions review outlines potential and, importantly, emphasizes longitudinal analyses, which are needed accurately monitor dynamics cerebral inflammation. Such precise information place will required before interventions can considered evaluation. We propose an effective anti-neuroinflammatory should specifically while considering individual status patients.

Язык: Английский

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Current Understanding of the Physiopathology, Diagnosis and Therapeutic Approach to Alzheimer’s Disease

Biomedicines, Год журнала: 2021, Номер 9(12), С. 1910 - 1910

Опубликована: Дек. 14, 2021

Alzheimer’s disease (AD) is the most common cause of dementia. It characterized by cognitive decline and progressive memory loss. The aim this review was to update state knowledge on pathophysiological mechanisms, diagnostic methods therapeutic approach AD. Currently, amyloid cascade hypothesis remains leading theory in pathophysiology This states that amyloid-β (Aβ) deposition triggers a chemical events development AD antemortem diagnosis still based clinical parameters. Diagnostic procedures include fluid-based biomarkers such as those present cerebrospinal fluid plasma or imaging methods. armory available focuses symptom control four pillars: pharmacological treatment where acetylcholinesterase inhibitors stand out; under investigation which includes drugs focused Aβ pathology tau hyperphosphorylation; focusing risk factors diabetes; nonpharmacological treatments aimed at preventing treating symptoms through occupational therapy psychological help. largely unknown disease. Further research needed identify new therapies can prevent progression pathology.

Язык: Английский

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Dietary Plant Polyphenols as the Potential Drugs in Neurodegenerative Diseases: Current Evidence, Advances, and Opportunities

Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 40

Опубликована: Фев. 21, 2022

Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's (PD), and Huntington's (HD), are characterized by the progressive degeneration of neurons. Although etiology pathogenesis neurodegenerative diseases have been studied intensively, mechanism is still in its infancy. In general, most share common molecular mechanisms, multiple risks interact promote pathologic process neurogenerative diseases. At present, approved drugs only alleviate clinical symptoms but fail to cure Numerous studies indicate that dietary plant polyphenols safe exhibit potent neuroprotective effects various However, low bioavailability biggest obstacle for polyphenol largely limits adoption from evidence into practice. this review, we summarized widely recognized mechanisms associated with such as misfolded proteins, mitochondrial dysfunction, oxidative damage, neuroinflammatory responses. addition, research advances about effect reported polyphenols. Moreover, discussed current study application factors result bioavailability, poor stability permeability across blood-brain barrier (BBB). future, improvement absorption stability, modification structure formulation, combination therapy will provide more opportunities laboratory clinic Lastly, hope present review encourage further researches on natural treatment

Язык: Английский

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Neuroinflammation as a Potential Therapeutic Target in Alzheimer’s Disease

Clinical Interventions in Aging, Год журнала: 2022, Номер Volume 17, С. 665 - 674

Опубликована: Апрель 1, 2022

Abstract: Although amyloid-β (Aβ) peptide accumulation is considered as a key early event in the pathogenesis of Alzheimer’s disease (AD), precise pathophysiology this deadly illness remains unclear and no effective remedies capable inhibiting progression have been discovered. In addition to deposition extracellular Aβ plaques intracellular neurofibrillary tangles, neuroinflammation has identified third core characteristic crucial AD. More more evidence from laboratory clinical studies suggested that anti-inflammatory treatments could defer or prevent occurrence review, we will discuss multifaceted presented AD newly emerged targets both pre-clinical Keywords: disease, neuroinflammation, disease‐modifying therapy, treatment

Язык: Английский

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Recent advancement in therapeutic strategies for Alzheimer’s disease: Insights from clinical trials

Ageing Research Reviews, Год журнала: 2023, Номер 92, С. 102113 - 102113

Опубликована: Ноя. 1, 2023

Язык: Английский

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C3N nanodots inhibits Aβ peptides aggregation pathogenic path in Alzheimer’s disease

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Сен. 15, 2023

Despite the accumulating evidence linking development of Alzheimer's disease (AD) to aggregation Aβ peptides and emergence oligomers, FDA has approved very few anti-aggregation-based therapies over past several decades. Here, we report discovery an peptide inhibitor: ultra-small nanodot called C3N. C3N nanodots alleviate aggregation-induced neuron cytotoxicity, rescue neuronal death, prevent neurite damage in vitro. Importantly, they reduce global cerebral levels, particularly fibrillar amyloid plaques, restore synaptic loss AD mice. Consequently, these significantly ameliorate behavioral deficits APP/PS1 double transgenic male Moreover, analysis critical tissues (e.g., heart, liver, spleen, lung, kidney) display no obvious pathological damage, suggesting are biologically safe. Finally, molecular dynamics simulations also reveal inhibitory mechanisms its potential application against AD.

Язык: Английский

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Comparative Efficacy and Safety of Monoclonal Antibodies for Cognitive Decline in Patients with Alzheimer’s Disease: A Systematic Review and Network Meta-Analysis

CNS Drugs, Год журнала: 2024, Номер 38(3), С. 169 - 192

Опубликована: Март 1, 2024

Язык: Английский

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