Role of neuroinflammation in neurodegeneration development

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 12, 2023

Abstract Studies in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis, Huntington’s so on, have suggested that inflammation is not only a result of neurodegeneration but also crucial player this process. Protein aggregates which are very common pathological phenomenon can induce neuroinflammation further aggravates protein aggregation neurodegeneration. Actually, even happens earlier than aggregation. Neuroinflammation induced by genetic variations CNS cells or peripheral immune may deposition some susceptible population. Numerous signaling pathways range been to be involved the pathogenesis neurodegeneration, although they still far from being completely understood. Due limited success traditional treatment methods, blocking enhancing inflammatory considered promising strategies for therapy many them got exciting results animal models clinical trials. Some them, few, approved FDA usage. Here we comprehensively review factors affecting major pathogenicity sclerosis. We summarize current strategies, both clinic, diseases.

Language: Английский

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Mitochondria: It is all about energy

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: April 25, 2023

Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron calcium homeostasis the of hormones neurotransmitters, such as melatonin. They enable influence communication at all physical levels through interaction with other organelles, nucleus, outside environment. The literature suggests crosstalk between mitochondria circadian clocks, gut microbiota, immune system. might even be hub supporting integrating activity across these domains. Hence, they (missing) link Mitochondrial dysfunction related metabolic syndrome, neuronal diseases, cancer, cardiovascular infectious inflammatory disorders. In this regard, diseases Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), pain are discussed. This review focuses on understanding mitochondrial action that allow for maintenance pathways toward dysregulated mechanisms. Although have allowed us adapt changes over course evolution, turn, evolution has shaped mitochondria. Each evolution-based intervention influences its own way. use physiological stress triggers tolerance stressor, achieving adaptability resistance. describes strategies could recover functioning providing comprehensive, root-cause-focused, integrative approach recovering treating people suffering diseases.

Language: Английский

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Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer’s disease

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(10), P. 1704 - 1721.e6

Published: Aug. 21, 2023

Circadian disruptions impact nearly all people with Alzheimer's disease (AD), emphasizing both their potential role in pathology and the critical need to investigate therapeutic of circadian-modulating interventions. Here, we show that time-restricted feeding (TRF) without caloric restriction improved key components including behavioral timing, pathology, hippocampal transcription, memory two transgenic (TG) mouse models AD. We found TRF had remarkable capability simultaneously reducing amyloid deposition, increasing Aβ42 clearance, improving sleep memory, normalizing daily transcription patterns multiple genes, those associated AD neuroinflammation. Thus, our study unveils for first time pleiotropic nature timed on AD, which has far-reaching effects beyond metabolism, ameliorating neurodegeneration misalignment circadian rhythmicity. Since can substantially modify trajectory, this intervention immediate translational potential, addressing urgent demand accessible approaches reduce or halt progression.

Language: Английский

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Pathogenesis of Neurodegenerative Diseases and the Protective Role of Natural Bioactive Components

Journal of the American Nutrition Association, Journal Year: 2023, Volume and Issue: 43(1), P. 20 - 32

Published: May 15, 2023

Neurodegenerative diseases are a serious problem throughout the world. There several causes of neurodegenerative diseases; these include genetic predisposition, accumulation misfolded proteins, oxidative stress, neuroinflammation, and excitotoxicity. Oxidative stress increases production reactive oxygen species (ROS) that advance lipid peroxidation, DNA damage, neuroinflammation. The cellular antioxidant system (superoxide dismutase, catalase, peroxidase, reduced glutathione) plays crucial role in scavenging free radicals. An imbalance defensive actions antioxidants overproduction ROS intensify neurodegeneration. formation glutamate toxicity, cytokine promote pathogenesis Alzheimer's disease, Parkinson's Huntington's amyotrophic lateral sclerosis. Antioxidants now attractive molecules to fight against Certain vitamins (A, E, C) polyphenolic compounds (flavonoids) show excellent properties. Diet is major source antioxidants. However, diet medicinal herbs also rich sources numerous flavonoids. prevent ROS-mediated neuronal degeneration post-oxidative conditions. present review focused on protective KEY TEACHING POINTSThis shows multiple factors directly or indirectly associated with diseases.Failure capacity intensifies neuroinflammation disease progression.Different vitamins, carotenoids, flavonoids, having capacity, can be considered agents.

Language: Английский

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Modulation of the Circadian Rhythm and Oxidative Stress as Molecular Targets to Improve Vascular Dementia: A Pharmacological Perspective

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4401 - 4401

Published: April 16, 2024

The circadian rhythms generated by the master biological clock located in brain's hypothalamus influence central physiological processes. At molecular level, a core set of genes interact to form transcription-translation feedback loops that provide basis rhythm. In animal models disease, desynchronization peripheral tissues with has been detected. Interestingly, patients vascular dementia have sleep disorders and irregular patterns. These alterations impact hormonal levels, cardiovascular health (including blood pressure regulation vessel function), pattern expression activity antioxidant enzymes. Additionally, oxidative stress can arise from ischemia-reperfusion injury, amyloid-beta production, abnormal phosphorylation tau protein, neurotransmitters, among others. Several signaling pathways are involved pathogenesis dementia. While precise mechanisms linking still being studied, there is evidence suggest maintaining healthy patterns supporting proper rhythm function may be important for reducing risk Here, we reviewed main action targets related cycle

Language: Английский

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It’s About Time: The Circadian Network as Time-Keeper for Cognitive Functioning, Locomotor Activity and Mental Health

Frontiers in Physiology, Journal Year: 2022, Volume and Issue: 13

Published: April 25, 2022

A variety of organisms including mammals have evolved a 24h, self-sustained timekeeping machinery known as the circadian clock (biological clock), which enables to anticipate, respond, and adapt environmental influences such daily light dark cycles. Proper functioning plays pivotal role in temporal regulation wide range cellular, physiological, behavioural processes. The disruption rhythms was found be associated with onset progression several pathologies sleep mental disorders, cancer, neurodegeneration. Thus, health disease, its clinical applications, gained increasing attention, but exact mechanisms underlying require further work integration evidence from different research fields. In this review, we address current knowledge regarding molecular circuits generators essential synchrony healthy organism. particular, discuss context behaviour cognitive functioning, delineating how loss tight interplay is linked pathological development focus on disorders We describe emerging new aspects link between physical exercise-induced usage activator positive impact delaying certain neurodegeneration brain-related disorders. Finally, recent epidemiological pointing an important health.

Language: Английский

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Circadian regulation in aging: Implications for spaceflight and life on earth

Aging Cell, Journal Year: 2023, Volume and Issue: 22(9)

Published: July 26, 2023

Abstract Alterations in the circadian system are characteristic of aging on Earth. With decline physiological processes due to aging, several health concerns including vision loss, cardiovascular disorders, cognitive impairments, and muscle mass loss arise elderly populations. Similar risks reported as “red flag” among astronauts during after a long‐term Space exploration journey. However, little is known about common molecular alterations underlying terrestrial space‐related astronauts, controversial conclusions have been recently reported. In light regulatory role clock maintenance human health, we review here overlapping both Earth spaceflight with focus four most affected systems: visual, cardiovascular, central nervous, musculoskeletal systems. this review, briefly introduce specific cellular followed by those aging. We next summarize associated spaceflight, highlighting involved clock‐regulated genes space flown Drosophila , nematodes, small mammals, astronauts. Finally, discuss that altered terms their expression spaceflight. Altogether, data elaborated strengthen our hypothesis regarding timely need include dysregulation an emerging hallmark beyond.

Language: Английский

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The Implementation of Infant Anoesis and Adult Autonoesis in the Retrogenesis and Staging System of the Neurocognitive Disorders: A Proposal for a Multidimensional Person-Centered Model

Geriatrics, Journal Year: 2025, Volume and Issue: 10(1), P. 20 - 20

Published: Feb. 2, 2025

Background: Retrogenesis is the process by which degenerative and vascular mechanisms of dementia reverse order acquisition in normal development. Objective: The development memory/knowledge after birth may help to know biopsychosocial functional characteristics (biosphere) retrogenesis. Methods: A literature review was performed PubMed, Google Scholar, Scopus databases using 43 keywords related retrogenesis: 234 eligible records were selected. Results: infantile amnesia, characterized from anoesis, described along infant/child's biosphere limbic system progressively develops body knowledge (Anoetic Body Consciousness, AnBC). Anoesis infant memory state absence long-term memories many stressful/painful experiences that accompany under long-life voluntary control fundamental for growth survival (mainly chewing/swallowing walking). At age 3-4 years, usually, AnBC evolves, as a continuum, into adulthood autonoesis with emergence, child/adolescent, consciousness "self" trough Episodic Autobiographic Memory (EAM) Autonoetic Mind Consciousness (AuMC). cognition due progressive maturation whole not only hippocampus. In retrogenesis, EAM/AuMC vanishes mild, moderate, severe stages when resurfaces, losing basic activities daily living retrogenetic where last functions disappear are chewing/swallowing. Conclusion: transition adult EAM-AuMC AnBC, continuum individual biosphere, adds contribution assessment retrogenesis multidimensional person-centered model.

Language: Английский

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Nanoparticles targeting the central circadian clock: Potential applications for neurological disorders

Advanced Drug Delivery Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 115561 - 115561

Published: March 1, 2025

Circadian rhythms and their involvement with various human diseases, including neurological disorders, have become an intense area of research for the development new pharmacological treatments. The location circadian clock machinery in central nervous system makes it challenging to reach molecular targets at therapeutic concentrations. In addition, a timely administration agents is necessary efficiently modulate clock. Thus, use nanoparticles dysfunctions may accelerate clinical translation by addressing these two key challenges: enhancing brain penetration and/or enabling formulation chronodelivery systems. This review describes implications pathologies, reviews potential modulators suggests how nanoparticle-based formulations could improve success. Finally, integration into chronopharmaceutical drug delivery systems will be described.

Language: Английский

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Challenges and Opportunities of Targeting Astrocytes to Halt Neurodegenerative Disorders

Cells, Journal Year: 2021, Volume and Issue: 10(8), P. 2019 - 2019

Published: Aug. 7, 2021

Neurodegenerative diseases are a heterogeneous group of disorders whose incidence is likely to duplicate in the next 30 years along with progressive aging western population. Non-cell-specific therapeutics or designed tackle aberrant pathways within neurons failed slow down halt neurodegeneration. Yet, last few years, our knowledge importance glial cells maintain central nervous system homeostasis health conditions has increased exponentially, awareness their fundamental and multifaced role pathological conditions. Among cells, astrocytes emerge as promising therapeutic targets various neurodegenerative disorders. In this review, we present latest evidence showing astonishing level specialization that display fulfill demands neuronal partners well plasticity upon injury. Then, discuss controversies fuel current debate on these cells. We potential beneficial effect cell therapy, achieved by transplanting precursors. Afterwards, introduce different strategies proposed modulate astrocyte functions neurodegeneration, ranging from lifestyle changes environmental cues. Finally, challenges recent advancements develop astrocyte-specific delivery systems.

Language: Английский

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