Mitochondria in the Central Nervous System in Health and Disease: The Puzzle of the Therapeutic Potential of Mitochondrial Transplantation

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 410 - 410

Published: Feb. 27, 2024

Mitochondria, the energy suppliers of cells, play a central role in variety cellular processes essential for survival or leading to cell death. Consequently, mitochondrial dysfunction is implicated numerous general and CNS disorders. The clinical manifestations include metabolic disorders, immune system, tumorigenesis, neuronal behavioral abnormalities. In this review, we focus on CNS, which has unique characteristics therefore highly dependent mitochondria. First, review mitochondria development, synaptogenesis, plasticity, behavior as well their adaptation intricate connections between different types brain. Then, sparse knowledge mechanisms exogenous uptake describe attempts determine half-life transplantation long-term effects sprouting, proteome, behavior. We further discuss potential serve tool study causal link activity Next, transplantation’s therapeutic various Finally, basic reverse—translation challenges approach that currently hinder use transplantation.

Language: Английский

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Targeting organ-specific mitochondrial dysfunction to improve biological aging

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 262, P. 108710 - 108710

Published: Aug. 22, 2024

In an aging society, unveiling new anti-aging strategies to prevent and combat aging-related diseases is of utmost importance. Mitochondria are the primary ATP production sites key regulators programmed cell death. Consequently, these highly dynamic organelles play a central role in maintaining tissue function, mitochondrial dysfunction pivotal factor progressive age-related decline cellular homeostasis organ function. The current review examines recent advances understanding interplay between organ-specific aging. Thereby, we dissect molecular mechanisms underlying impairment associated with deterioration exploring DNA, reactive oxygen species homeostasis, metabolic activity, damage-associated patterns, biogenesis, turnover, dynamics. We also highlight emerging therapeutic preclinical clinical tests that supposed rejuvenate such as antioxidants, biogenesis stimulators, modulators turnover Furthermore, discuss potential benefits challenges use interventions, emphasizing need for approaches given unique characteristics different tissues. conclusion, this highlights addressing mitigate aging, focusing on skin, liver, lung, brain, skeletal muscle, well reproductive, immune, cardiovascular systems. Based comprehensive multifaceted roles mitochondria, innovative may be developed optimized biological promote healthy across diverse

Language: Английский

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The emerging role of brain neuroinflammatory responses in Alzheimer’s disease

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: July 3, 2024

As the most common cause of dementia, Alzheimer’s disease (AD) is characterized by neurodegeneration and synaptic loss with an increasing prevalence in elderly. Increased inflammatory responses triggers brain cells to produce pro-inflammatory cytokines accelerates Aβ accumulation, tau protein hyper-phosphorylation leading neurodegeneration. Therefore, this paper, we discuss current understanding how inflammation affects activity induce AD pathology, biomarkers possible therapies that combat for AD.

Language: Английский

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The neuroinflammatory role of microglia in Alzheimer's disease and their associated therapeutic targets

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(7)

Published: July 1, 2024

Abstract Introduction Alzheimer's disease (AD), the main cause of dementia, is characterized by synaptic loss and neurodegeneration. Amyloid‐β (Aβ) accumulation, hyperphosphorylation tau protein, neurofibrillary tangles (NFTs) in brain are considered to be initiating factors AD. However, this hypothesis falls short explaining many aspects AD pathogenesis. Recently, there has been mounting evidence that neuroinflammation plays a key role pathophysiology causes neurodegeneration over‐activating microglia releasing inflammatory mediators. Methods PubMed, Web Science, EMBASE, MEDLINE were used for searching summarizing all recent publications related inflammation its association with disease. Results Our review shows how dysregulation influences pathology as well roles neuroinflammation, possible microglia‐associated therapeutic targets, top neuroinflammatory biomarkers, anti‐inflammatory drugs combat inflammation. Conclusion In conclusion, microglial reactions important pathogenesis need discussed more detail promising strategies.

Language: Английский

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Vicious cycle of oxidative stress and neuroinflammation in pathophysiology of chronic vascular encephalopathy

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 5, 2024

Chronic vascular encephalopathy (CVE) is a frequent cause of mild cognitive impairment and dementia, which significantly worsens the quality life, especially in elderly population. CVE result chronic cerebral hypoperfusion, characterized by prolonged limited blood flow to brain. This causes insufficient oxygenation brain leading hypoxia. The latter can trigger series events associated with development oxidative/reductive stresses neuroinflammation. Addressing gap knowledge regarding oxidative reductive disorders neuroinflammation give start new directions research context CVE. In this review, we consider hypoxia-induced molecular challenges involved pathophysiology CVE, focusing on stress neuroinflammation, are combined vicious cycle neurodegeneration. We also briefly describe therapeutic approaches treatment outline prospects for use sulforaphane, an isothiocyanate common cruciferous plants, vitamin D break alleviate impairments characteristic patients

Language: Английский

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Mitochondrial dysfunction gene expression, DNA methylation, and inflammatory cytokines interaction activate Alzheimer’s disease: a multi-omics Mendelian randomization study

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 3, 2024

Mitochondrial dysfunction (MD) is increasingly recognized as a key pathophysiological contributor in Alzheimer disease (AD). As differential MD genes expression may serve either causative factor or consequence AD, and of these could be influenced by epigenetic modifications interact with inflammatory cytokines, hence, the precise role AD remains uncertain.

Language: Английский

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Mitochondrial Dysfunction is a Crucial Immune Checkpoint for Neuroinflammation and Neurodegeneration: mtDAMPs in Focus

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

Published: Aug. 8, 2024

Language: Английский

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Two- and Three-Dimensional In Vitro Models of Parkinson’s and Alzheimer’s Diseases: State-of-the-Art and Applications

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 620 - 620

Published: Jan. 13, 2025

In vitro models play a pivotal role in advancing our understanding of neurodegenerative diseases (NDs) such as Parkinson’s and Alzheimer’s disease (PD AD). Traditionally, 2D cell cultures have been instrumental elucidating the cellular mechanisms underlying these diseases. Cultured cells derived from patients or animal provide valuable insights into pathological processes at level. However, they often lack native tissue environment complexity, limiting their ability to fully recapitulate features. contrast, 3D offer more physiologically relevant platform by mimicking brain architecture. These can incorporate multiple types, including neurons, astrocytes, microglia, creating microenvironment that closely resembles brain’s complexity. Bioengineering approaches allow researchers better replicate cell–cell interactions, neuronal connectivity, disease-related phenotypes. Both advantages limitations. While simplicity scalability for high-throughput screening basic processes, enhanced physiological relevance Integrating findings both model systems NDs, ultimately aiding development novel therapeutic strategies. Here, we review existing study PD AD.

Language: Английский

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Alzheimer’s Disease: Exploring Pathophysiological Hypotheses and the Role of Machine Learning in Drug Discovery

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1004 - 1004

Published: Jan. 24, 2025

Alzheimer’s disease (AD) is a major neurodegenerative dementia, with its complex pathophysiology challenging current treatments. Recent advancements have shifted the focus from traditionally dominant amyloid hypothesis toward multifactorial understanding of disease. Emerging evidence suggests that while amyloid-beta (Aβ) accumulation central to AD, it may not be primary driver but rather part broader pathogenic process. Novel hypotheses been proposed, including role tau protein abnormalities, mitochondrial dysfunction, and chronic neuroinflammation. Additionally, gut–brain axis epigenetic modifications gained attention as potential contributors AD progression. The limitations existing therapies underscore need for innovative strategies. This study explores integration machine learning (ML) in drug discovery accelerate identification novel targets candidates. ML offers ability navigate AD’s complexity, enabling rapid analysis extensive datasets optimizing clinical trial design. synergy between these themes presents promising future more effective

Language: Английский

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The Role of Small Extracellular Vesicles Derived from Glial Cells in the Central Nervous System under both Normal and Pathological Conditions

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(2)

Published: Jan. 30, 2025

Language: Английский

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