Role of Microglia and Astrocytes in Alzheimer’s Disease: From Neuroinflammation to Ca2+ Homeostasis Dysregulation

Cells, Journal Year: 2022, Volume and Issue: 11(17), P. 2728 - 2728

Published: Sept. 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.

Language: Английский

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Mitochondria and Brain Disease: A Comprehensive Review of Pathological Mechanisms and Therapeutic Opportunities

Biomedicines, Journal Year: 2023, Volume and Issue: 11(9), P. 2488 - 2488

Published: Sept. 7, 2023

Mitochondria play a vital role in maintaining cellular energy homeostasis, regulating apoptosis, and controlling redox signaling. Dysfunction of mitochondria has been implicated the pathogenesis various brain diseases, including neurodegenerative disorders, stroke, psychiatric illnesses. This review paper provides comprehensive overview intricate relationship between disease, focusing on underlying pathological mechanisms exploring potential therapeutic opportunities. The covers key topics such as mitochondrial DNA mutations, impaired oxidative phosphorylation, dynamics, calcium dysregulation, reactive oxygen species generation context disease. Additionally, it discusses emerging strategies targeting dysfunction, protective agents, metabolic modulators, gene therapy approaches. By critically analysing existing literature recent advancements, this aims to enhance our understanding multifaceted disease shed light novel interventions.

Language: Английский

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Single nucleus multiomics identifies ZEB1 and MAFB as candidate regulators of Alzheimer’s disease-specific cis-regulatory elements

Cell Genomics, Journal Year: 2023, Volume and Issue: 3(3), P. 100263 - 100263

Published: Feb. 2, 2023

Cell type-specific transcriptional differences between brain tissues from donors with Alzheimer's disease (AD) and unaffected controls have been well documented, but few studies rigorously interrogated the regulatory mechanisms responsible for these alterations. We performed single nucleus multiomics (snRNA-seq plus snATAC-seq) on 105,332 nuclei isolated cortical 7 AD 8 to identify candidate

Language: Английский

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Trace Elements in Alzheimer’s Disease and Dementia: The Current State of Knowledge

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(8), P. 2381 - 2381

Published: April 19, 2024

Changes in trace element concentrations are being wildly considered when it comes to neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. This study aims present the role that elements play central nervous system. Moreover, we reviewed mechanisms involved their neurotoxicity. Low zinc concentrations, well high levels of copper, manganese, iron, activate signalling pathways inflammatory, oxidative nitrosative stress response. Neurodegeneration occurs due association between metals proteins, which is then followed by aggregate formation, mitochondrial disorder, and, ultimately, cell death. In disease, low Zn suppress neurotoxicity induced β-amyloid through selective precipitation aggregation intermediates. High iron manganese cause intracellular α-synuclein, results synaptic dysfunction axonal transport disruption. caused accumulation Fe midbrain dopaminergic nucleus, pathogenesis multiple sclerosis derives from deficiency, leading an imbalance T functions. Aluminium disturbs homeostasis other a rise production oxygen reactive forms, leads cellular Selenium, with plays distinct process ferroptosis. Outlining influence have on oxidoreduction processes crucial recognising pathophysiology diseases may provide possible new methods for both avoidance therapy.

Language: Английский

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Altered Metabolism in Alzheimer Disease Brain: Role of Oxidative Stress

Antioxidants and Redox Signaling, Journal Year: 2021, Volume and Issue: 36(16-18), P. 1289 - 1305

Published: Aug. 21, 2021

Significance: Alzheimer disease (AD) is an all-too-common condition in the aging population. However, does not automatically equal neurodegeneration and memory decline. Recent Advances: This review article involves metabolic changes AD brain that are related to oxidative stress. Selected pathways identified as potential targets for intervention AD. Critical Issues: One of main factors imbalance within central nervous system, causing a disruption processes. Reactive oxygen species (ROS) natural consequence many cellular processes, especially those associated with mitochondria, such electron transport chain. Some ROS, when kept under control maintained at reasonable levels, often play roles cell signaling. The damage ROS arises occurs, which case controlled, leading myriad alterations These altered include, among others, dysfunctional glycolysis, calcium regulation, lipid metabolism, mitochondrial mammalian target rapamycin pathway dysregulation. Future Directions: Understanding how can lead these can, ideally, elucidate therapeutic options retarding progression Antioxid. Redox Signal. 36, 1289-1305.

Language: Английский

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Astrocytes as a Therapeutic Target in Alzheimer’s Disease–Comprehensive Review and Recent Developments

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 13630 - 13630

Published: Nov. 7, 2022

Alzheimer’s disease (AD) is a frequent and disabling neurodegenerative disorder, in which astrocytes participate several pathophysiological processes including neuroinflammation, excitotoxicity, oxidative stress lipid metabolism (along with critical role apolipoprotein E function). Current evidence shows that have both neuroprotective neurotoxic effects depending on the stage microenvironmental factors. Furthermore, appear to be affected by presence of amyloid-beta (Aβ), alterations calcium levels, gliotransmission proinflammatory activity via RAGE-NF-κB pathway. In addition, play an important tau clearance Aβ through glymphatic system. this review, we will discuss novel pharmacological non-pharmacological treatments focused as therapeutic targets for AD. These interventions include anti-inflammatory/antioxidant systems, glutamate activity, metabolism, neurovascular coupling system, dysregulation, release peptides affects glial neuronal function. According AD stage, these therapies may benefit either preventing or delaying progression disease.

Language: Английский

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Liquid crystalline lipid nanoparticles for combined delivery of curcumin, fish oil and BDNF: In vitro neuroprotective potential in a cellular model of tunicamycin-induced endoplasmic reticulum stress

Smart Materials in Medicine, Journal Year: 2022, Volume and Issue: 3, P. 274 - 288

Published: Jan. 1, 2022

We develop multidrug-loaded cubosome and spongosome lipid nanoparticles for targeting of endoplasmic reticulum stress as a potential emerging therapeutic strategy against neuronal degeneration. The multicompartment organization the liquid crystalline (LCNPs), fabricated by self-assembly, was characterized cryogenic transmission electron microscopy (cryo-TEM) small-angle X-ray scattering (SAXS). Monoolein-based LCNPs co-encapsulated natural plant-derived antioxidant curcumin, fish oil rich in ω-3 polyunsaturated fatty acids (PUFA), neurotrophin brain-derived neurotrophic factor (BDNF), which is vital need neurogenesis. neuroprotective properties were vitro investigated cellular model tunicamycin-induced (ER) using differentiated human neuroblastoma SH-SY5Y cells deprieved from serum. intracellular accumulation aggregates misfolded proteins, typical ER process, analyzed fluorescence co-localization imaging staining. performed bioassays established that BDNF-loaded enhanced cell survival. diminution upon internalization quantified via changes Thioflavin T fluorescence, sensitive marker protein aggregation. with multi-drug loading appear to be promising candidates face challenges nanomedicine development exploiting ER-stress mechanisms.

Language: Английский

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The role of mitochondrial dysfunction in Alzheimer's disease: A potential pathway to treatment

Experimental Gerontology, Journal Year: 2022, Volume and Issue: 164, P. 111828 - 111828

Published: May 1, 2022

Language: Английский

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Integrative metabolomics science in Alzheimer’s disease: Relevance and future perspectives

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 89, P. 101987 - 101987

Published: June 19, 2023

Language: Английский

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The Role of Oxygen Homeostasis and the HIF-1 Factor in the Development of Neurodegeneration

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4581 - 4581

Published: April 23, 2024

Understanding the molecular underpinnings of neurodegeneration processes is a pressing challenge for medicine and neurobiology. Alzheimer’s disease (AD) Parkinson’s (PD) represent most prevalent forms neurodegeneration. To date, substantial body experimental evidence has strongly implicated hypoxia in pathogenesis numerous neurological disorders, including AD, PD, other age-related neurodegenerative conditions. Hypoxia-inducible factor (HIF) transcription that triggers cell survival program conditions oxygen deprivation. The involvement HIF-1α presents complex sometimes contradictory picture. This review aims to elucidate current understanding interplay between development AD assess HIF-1 their pathogenesis, summarize promising therapeutic approaches centered on modulating activity complex.

Language: Английский

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