The Molecular Clock and Neurodegenerative Disease: A Stressful Time DOI Creative Commons

Bethany Carter,

Hannah Justin,

Danielle Gulick

et al.

Frontiers in Molecular Biosciences, Journal Year: 2021, Volume and Issue: 8

Published: March 26, 2021

Circadian rhythm dysfunction occurs in both common and rare neurodegenerative diseases. This manifests as sleep cycle mistiming, alterations body temperature rhythms, an increase symptomatology during the early evening hours known Sundown Syndrome. Disruption of circadian homeostasis has also been implicated etiology disease. Indeed, individuals exposed to a shifting schedule activity, such health care workers, are at higher risk. Thus, bidirectional relationship exists between system neurodegeneration. At heart this crosstalk is molecular clock, which functions regulate homeostasis. Over past decade, connection become focal point investigation clock offers attractive target combat disease pathogenesis dysfunction, pivotal role for neuroinflammation stress established. review summarizes contributions etiology, well mechanisms by diseases affect clock.

Language: Английский

Synchrony and desynchrony in circadian clocks: impacts on learning and memory DOI Open Access

Harini C. Krishnan,

Lisa C. Lyons

Learning & Memory, Journal Year: 2015, Volume and Issue: 22(9), P. 426 - 437

Published: Aug. 18, 2015

Circadian clocks evolved under conditions of environmental variation, primarily alternating light dark cycles, to enable organisms anticipate daily events and coordinate metabolic, physiological, behavioral activities. However, modern lifestyle advances in technology have increased the percentage individuals working phases misaligned with natural circadian activity rhythms. Endogenous oscillators modulate alertness, acquisition learning, memory formation, recall examples modulation observed across phyla from invertebrates humans. Cognitive performance are significantly diminished when occurring out phase Disruptions regulation can lead impairment formation memories manifestation other cognitive deficits. This review explores types interactions through which clock modulates cognition, highlights recent progress identifying mechanistic between system processes involved outlines methods used remediate perturbations reinforce adaptation.

Language: Английский

Citations

88
Reciprocal Control of the Circadian Clock and Cellular Redox State - a Critical Appraisal DOI Creative Commons
Marrit Putker, John S. O’Neill

Molecules and Cells, Journal Year: 2016, Volume and Issue: 39(1), P. 6 - 19

Published: Jan. 1, 2016

Redox signalling comprises the biology of molecular signal transduction mediated by reactive oxygen (or nitrogen) species. By specific and reversible oxidation redoxsensitive cysteines, many biological processes sense respond to signals from intracellular redox environment. are therefore important regulators cellular homeostasis. Recently, it has become apparent that state oscillates in vivo vitro, with a period about one day (circadian). Circadian timekeeping allows cells organisms adapt their resonate 24-hour cycle day/night. The importance this innate is illustrated association clock disruption early onset several diseases (e.g. type II diabetes, stroke forms cancer). regulation balance suggests potentially two distinct roles for relation clock: where regulated clock, regulates clock. Here, we introduce concepts timekeeping, then critically appraise evidence reciprocal between circadian clock.We conclude there substantial body supporting state, but would be premature converse also true.We propose some approaches might yield more insight into control timekeeping. INTRODUCTIONIntracellular determines direction reactions occur cell, determined pro-oxidants compared antioxidants.Oxidising conditions result an increase levels pro-oxidant species (ROS, or RNS) decrease reducing power.Although high ROS (a known as oxidative

Language: Английский

Citations

76
Sleep and Neurodegeneration DOI
Jagan A. Pillai, James B. Leverenz

CHEST Journal, Journal Year: 2017, Volume and Issue: 151(6), P. 1375 - 1386

Published: Jan. 10, 2017

Language: Английский

Citations

65
Actigraphy‐estimated sleep and 24‐hour activity rhythms and the risk of dementia DOI Creative Commons
Thom S. Lysen, Annemarie I. Luik, M. Kamran Ikram

et al.

Alzheimer s & Dementia, Journal Year: 2020, Volume and Issue: 16(9), P. 1259 - 1267

Published: June 19, 2020

Abstract Introduction We investigated and compared associations of objective estimates sleep 24‐hour activity rhythms using actigraphy with risk dementia. Methods included 1322 non‐demented participants from the prospective, population‐based Rotterdam Study cohort valid data (mean age 66 ± 8 years, 53% women), followed them for up to 11.2 years determine incident Results During follow‐up, 60 individuals developed dementia, which 49 had Alzheimer's disease (AD). Poor as indicated by longer latency, wake after onset, time in bed lower efficiency, well an earlier “lights out” time, were associated increased especially AD. found no dementia risk. Discussion sleep, but not rhythm disturbance, is Actigraphy‐estimated nighttime wakefulness may be further targeted etiologic or prediction studies.

Language: Английский

Citations

52
Transcriptomic Profiling Reveals Neuroinflammation in the Corpus Callosum of a Transgenic Mouse Model of Alzheimer’s Disease DOI
Hajime Takase,

Gen Hamanaka,

Tomonori Hoshino

et al.

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 97(3), P. 1421 - 1433

Published: Jan. 23, 2024

Background: Alzheimer’s disease (AD) is a widespread neurodegenerative disorder characterized by progressive cognitive decline, affecting significant portion of the aging population. While cerebral cortex and hippocampus have been primary focus AD research, accumulating evidence suggests that white matter lesions in brain, particularly corpus callosum, play an important role pathogenesis disease. Objective: This study aims to investigate gene expression changes callosum 5xFAD transgenic mice, widely used mouse model. Methods: We conducted behavioral tests for spatial learning memory mice performed RNA sequencing analyses on examine transcriptomic changes. Results: Our results show decline demyelination mice. Transcriptomic analysis reveals predominance upregulated genes those associated with immune cells, including microglia. Conversely, downregulation related chaperone function clock such as Per1, Per2, Cry1 also observed. Conclusions: activation neuroinflammation, disruption function, circadian dysfunction are involved AD. The findings provide insights into potential therapeutic targets highlight importance addressing pathology treatment strategies.

Language: Английский

Citations

7
Day‐to‐day sleep variability with Alzheimer's biomarkers in at‐risk elderly DOI

Andrée‐Ann Baril,

Cynthia Picard, Anne Labonté

et al.

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 1, 2024

Language: Английский

Citations

6
Melatonin: a ferroptosis inhibitor with potential therapeutic efficacy for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration DOI Creative Commons
Asmaa Yehia, Osama A. Abulseoud

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: April 19, 2024

Abstract The unprecedented pandemic of COVID-19 swept millions lives in a short period, yet its menace continues among survivors the form post-COVID syndrome. An exponentially growing number suffer from cognitive impairment, with compelling evidence trajectory accelerated aging and neurodegeneration. novel enigmatic nature this yet-to-unfold pathology demands extensive research seeking answers for both molecular underpinnings potential therapeutic targets. Ferroptosis, an iron-dependent cell death, is strongly proposed underlying mechanism post-COVID-19 neurodegeneration discourse. incites neuroinflammation, iron dysregulation, reactive oxygen species (ROS) accumulation, antioxidant system repression, renin-angiotensin (RAS) disruption, clock gene alteration. These events pave way ferroptosis, which shows signature COVID-19, premature aging, neurodegenerative disorders. In search treatment, melatonin shines as promising ferroptosis inhibitor repeatedly reported safety tolerability. According to various studies, has proven efficacy attenuating severity certain manifestations, validating reputation anti-viral compound. Melatonin well-documented anti-aging properties combating neurodegenerative-related pathologies. can block leading since it efficient anti-inflammatory, chelator, antioxidant, angiotensin II antagonist, regulator. Therefore, we propose culprit behind melatonin, well-fitting inhibitor, treatment.

Language: Английский

Citations

6
Systemic Central Nervous System (CNS)-targeted Delivery of Neuropeptide Y (NPY) Reduces Neurodegeneration and Increases Neural Precursor Cell Proliferation in a Mouse Model of Alzheimer Disease DOI Creative Commons
Brian Spencer,

Rewati Potkar,

Jeff Metcalf

et al.

Journal of Biological Chemistry, Journal Year: 2015, Volume and Issue: 291(4), P. 1905 - 1920

Published: Dec. 1, 2015

Language: Английский

Citations

56
Implications of Circadian Rhythm in Dopamine and Mood Regulation DOI Creative Commons
Jeong‐Ah Kim,

Sang-Won Jang,

Han Kyoung Choe

et al.

Molecules and Cells, Journal Year: 2017, Volume and Issue: 40(7), P. 450 - 456

Published: July 1, 2017

Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm.The timing system has a hierarchical organization composed of the master clock in suprachiasmatic nucleus (SCN) local clocks extra-SCN brain regions peripheral organs.The molecular mechanism involves network transcription-translation feedback loops.In addition clinical association between rhythm disruption mood disorders, recent studies have suggested link regulation rhythm.Specifically, genetic deletion nuclear receptor Rev-erb induces mania-like caused increased midbrain dopaminergic (DAergic) tone at dusk.The emotion-related behaviors can be applied pathological conditions, including neurodegenerative diseases.In Parkinson's disease (PD), DAergic neurons substantia nigra pars compacta progressively degenerate leading motor dysfunction.Patients with PD also exhibit non-motor symptoms, sleep disorder neuropsychiatric disorders.Thus, it is important understand mechanisms that machinery emotional related neuronal circuits healthy states.This review summarizes current literature regarding from chronobiological perspective, may provide insight into therapeutic approaches target psychiatric symptoms diseases involving dysfunction.

Language: Английский

Citations

52
Sleep and circadian rhythm disruption and stress intersect in Alzheimer's disease DOI Creative Commons
Trongha Phan, Roneil G. Malkani

Neurobiology of Stress, Journal Year: 2018, Volume and Issue: 10, P. 100133 - 100133

Published: Oct. 17, 2018

Alzheimer's disease (AD) was discovered and the pathological hallmarks were revealed more than a century ago. Subsequently, many remarkable discoveries breakthroughs provided us with mechanistic insights into pathogenesis of AD. The identification molecular underpinning not only framework AD but also targets for therapeutic inventions. Despite all initial successes, no effective treatment has emerged yet as late stages clinical trials have failed. Many factors ranging from genetic to environmental been critically appraised potential causes In particular, role stress on intensively studied while relationship between sleep circadian rhythm disruption (SCRD) recently emerged. SCRD always thought be corollary pathologies until recently, multiple lines evidence converge notion that might contributing factor in pathogenesis. More importantly, how intersect make their concerted contributions phenotypes reviewed. goal this literature review is examine at levels - molecular, cellular (e.g. microglia, gut microbiota) holistic interaction bi-directionally synergistically exacerbate cognitive impairment. AD, turn, worsens forms vicious cycle perpetuates amplifies

Language: Английский

Citations

52