Retinal Alterations Predict Early Prodromal Signs of Neurodegenerative Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1689 - 1689

Опубликована: Янв. 30, 2024

Neurodegenerative diseases are an increasingly common group of that occur late in life with a significant impact on personal, family, and economic life. Among these, Alzheimer’s disease (AD) Parkinson’s (PD) the major disorders lead to mild severe cognitive physical impairment dementia. Interestingly, those may show onset prodromal symptoms early after middle age. Commonly, evaluation these neurodegenerative is based detection biomarkers, where functional structural magnetic resonance imaging (MRI) have shown central role revealing or phases, although it can be expensive, time-consuming, not always available. The aforementioned visual system due pathophysiological mechanisms shared between eye brain. In disease, α-synuclein deposition retinal cells, as well dopaminergic neurons substantia nigra, alters cortex function, resulting modifications field. Similarly, modified by neurofibrillary tangles neuritic amyloid β plaques typically seen brain, this reflect accumulation biomarkers retina during stages postmortem retinas AD patients. light, ophthalmic neurodegeneration could become cost-effective method for diagnosis diseases, overcoming limitations deep This analysis commonly used practice, interest has risen recent years. review will discuss relationship degeneration, highlighting how represent noninvasive straightforward diseases.

Язык: Английский

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Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System

Biomolecules, Год журнала: 2023, Номер 13(5), С. 816 - 816

Опубликована: Май 11, 2023

It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning knowledge that disease intimately tied to neurodegenerative disorders, affecting both central and peripheral nervous systems well leading dementia, seventh cause of death. New innovative therapeutic strategies address metabolism, apoptosis, autophagy, pyroptosis, mechanistic target rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), risk factors apolipoprotein E (APOE-ε4) gene coronavirus 2019 (COVID-19) can offer valuable insights for clinical care treatment disorders impacted by disease. Critical insight into modulation these complex pathways are required since mTOR pathways, AMPK activation, improve memory retention in Alzheimer's (AD) DM, promote healthy aging, facilitate clearance β-amyloid (Aß) tau brain, control inflammation, but also may lead cognitive loss long-COVID syndrome through mechanisms include oxidative stress, mitochondrial cytokine release, APOE-ε4 if autophagy other programmed cell death left unchecked.

Язык: Английский

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The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 8, 2023

Life expectancy is increasing throughout the world and coincides with a rise in non-communicable diseases (NCDs), especially for metabolic disease that includes diabetes mellitus (DM) neurodegenerative disorders. The debilitating effects of disorders influence entire body significantly affect nervous system impacting greater than one billion people disability peripheral as well cognitive loss, now seventh leading cause death worldwide. Metabolic disorders, such DM, neurologic remain significant challenge treatment care individuals since present therapies may limit symptoms but do not halt overall progression. These clinical challenges to address interplay between warrant innovative strategies can focus upon underlying mechanisms aging-related oxidative stress, cell senescence, death. Programmed pathways involve autophagy, apoptosis, ferroptosis, pyroptosis play critical role oversee processes include insulin resistance, β-cell function, mitochondrial integrity, reactive oxygen species release, inflammatory activation. silent mating type information regulation 2 homolog 1

Язык: Английский

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Sestrin2 ameliorates diabetic retinopathy by regulating autophagy and ferroptosis

Journal of Molecular Histology, Год журнала: 2024, Номер 55(2), С. 169 - 184

Опубликована: Янв. 2, 2024

Abstract Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. The aim this study was to explore the effect Sestrin2 on DR through regulation autophagy and ferroptosis levels its mechanism. In vitro in vivo models were established by high glucose (HG) streptozotocin (STZ) induction ARPE-19 human retinal pigment epithelial cells C57BL/6 mice, respectively. study, we demonstrated that after HG treatment, activity decreased, apoptosis rate increased, endoplasmic reticulum (ER) stress activated, increased. Overexpression enhanced cell viability, reduced ferroptosis, autophagy. However, overexpression attenuated addition STAT3 phosphorylation activator Colivelin TFA (C-TFA), mTOR pathway MHY1485 or inhibitor 3-methyladenine (3-MA). addition, knockdown opposite Sestrin2, while treatment with ER 4-phenylbutyric acid (4-PBA). Animal experiments also confirmed results effects injection activators erastin 3-MA. Our revealed inhibits inhibiting promoting levels, thereby alleviating DR.

Язык: Английский

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Microglia-endothelial cross-talk regulates diabetes-induced retinal vascular dysfunction through remodeling inflammatory microenvironment

iScience, Год журнала: 2024, Номер 27(3), С. 109145 - 109145

Опубликована: Фев. 6, 2024

Inflammation-mediated crosstalk between neuroglial cells and endothelial (ECs) is a fundamental feature of many vascular diseases. Nevertheless, the landscape inflammatory processes during diabetes-induced microvascular dysfunction remains elusive. Here, we applied single-cell RNA sequencing to elucidate transcriptional diabetic retinopathy (DR). The transcriptome characteristics microglia ECs revealed two microglial subpopulations three EC populations. Exploration intercellular showed that interactions mainly participated in response vessel development, with colony-stimulating factor 1 (CSF1) CSF1 receptor (CSF1R) playing important roles early cell differentiation. Clinically, found CSF1/CSF1R dysregulation was associated proliferative DR. Mechanistically, secrete activate CSF1R endocytosis phosphorylation-mediated MAPK signaling pathway, which elicits differentiation triggers secretion factors, subsequently foster angiogenesis by remodeling microenvironment through positive feedback mechanism.

Язык: Английский

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The Metabolic Basis for Nervous System Dysfunction in Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease

Current Neurovascular Research, Год журнала: 2023, Номер 20(3), С. 314 - 333

Опубликована: Июль 25, 2023

Disorders of metabolism affect multiple systems throughout the body but may have greatest impact on both central and peripheral nervous systems. Currently available treatments behavior changes for disorders that include diabetes mellitus (DM) system diseases are limited cannot reverse disease burden. Greater access to healthcare a longer lifespan led an increased prevalence metabolic neurodegenerative disorders. In light these challenges, innovative studies into underlying pathways offer new treatment perspectives Alzheimer's Disease, Parkinson's Huntington's Disease. Metabolic intimately tied can lead debilitating outcomes, such as multi-nervous disease, susceptibility viral pathogens, long-term cognitive disability. Novel strategies robustly address involve careful consideration cellular metabolism, programmed cell death pathways, mechanistic target rapamycin (mTOR) its associated mTOR Complex 1 (mTORC1), 2 (mTORC2), AMP-activated protein kinase (AMPK), growth factor signaling, risk factors apolipoprotein E (APOE-ε4) gene. Yet, complex necessitate comprehensive understanding achieve clinical outcomes susceptibility, onset, progression.

Язык: Английский

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Cognitive Impairment in Multiple Sclerosis

Bioengineering, Год журнала: 2023, Номер 10(7), С. 871 - 871

Опубликована: Июль 23, 2023

Almost three million individuals suffer from multiple sclerosis (MS) throughout the world, a demyelinating disease in nervous system with increased prevalence over last five decades, and is now being recognized as one significant etiology of cognitive loss dementia. Presently, modifying therapies can limit rate relapse potentially reduce brain volume patients MS, but unfortunately cannot prevent progression or onset disability. Innovative strategies are therefore required to address areas inflammation, immune cell activation, survival that involve novel pathways programmed death, mammalian forkhead transcription factors (FoxOs), mechanistic target rapamycin (mTOR), AMP activated protein kinase (AMPK), silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), associated apolipoprotein E (APOE-ε4) gene severe acute respiratory syndrome coronavirus (SARS-CoV-2). These intertwined at levels metabolic oversight cellular metabolism dependent upon nicotinamide adenine dinucleotide (NAD+). Insight into mechanisms these provide new avenues discovery for therapeutic treatment dementia cognition occurs during MS.

Язык: Английский

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Redox Regulation of Immunometabolism in Microglia Underpinning Diabetic Retinopathy

Antioxidants, Год журнала: 2024, Номер 13(4), С. 423 - 423

Опубликована: Март 29, 2024

Diabetic retinopathy (DR) is the leading cause of visual impairment and blindness among working-age population. Microglia, resident immune cells in retina, are recognized as crucial drivers DR process. Microglia activation a tightly regulated immunometabolic In early stages DR, M1 phenotype commonly shifts from oxidative phosphorylation to aerobic glycolysis for energy production. Emerging evidence suggests that microglia not only engage specific metabolic pathways but also rearrange their oxidation-reduction (redox) system. This redox adaptation supports reprogramming offers potential therapeutic strategies using antioxidants. Here, we provide an overview recent insights into involvement reactive oxygen species distinct roles played by key cellular antioxidant pathways, including NADPH oxidase 2 system, which promotes via enhanced glucose transporter 4 translocation cell membrane through AKT/mTOR pathway, well thioredoxin nuclear factor E2-related systems, maintain anti-inflammatory state. Therefore, highlight targeting modulation microglial metabolism offer new concepts treatment.

Язык: Английский

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State of the Art of Pharmacological Activators of p53 in Ocular Malignancies

Cancers, Год журнала: 2023, Номер 15(14), С. 3593 - 3593

Опубликована: Июль 12, 2023

The pivotal role of p53 in the regulation a vast array cellular functions has been subject extensive research. biological activity is not strictly limited to cell cycle arrest but also includes homeostasis, DNA repair, apoptosis, and senescence. Thus, mutations gene with loss function represent one major mechanisms for cancer development. As expected, due its key role, expressed throughout human body including eye. Specifically, altered signaling pathways have implicated development conjunctival corneal tumors, retinoblastoma, uveal melanoma, intraocular melanoma. non-selective chemotherapies as well ionizing radiation can be associated either poor efficacy or dose-limiting toxicities eye, reconstitution pathway currently represents an attractive target therapy. present review discusses pathogenesis these ocular tumors outlines various pharmacological activators that are under investigation treatment malignancies.

Язык: Английский

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The Implications of Telomere Length: Advanced Aging, Cell Senescence, MRI Phenotypes, Stem Cells and Alzheimer’s Disease

Current Neurovascular Research, Год журнала: 2023, Номер 20(2), С. 171 - 174

Опубликована: Май 1, 2023

Язык: Английский

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