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The Role of the Circadian Clock in Hippocampal Aging and as a Therapeutic Target in Alzheimer's Disease

2020
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Release : 2020
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Book Synopsis The Role of the Circadian Clock in Hippocampal Aging and as a Therapeutic Target in Alzheimer's Disease by : Paula Adler

Download or read book The Role of the Circadian Clock in Hippocampal Aging and as a Therapeutic Target in Alzheimer's Disease written by Paula Adler. This book was released on 2020. Available in PDF, EPUB and Kindle. Book excerpt: Aging-associated cognitive impairment and neurodegenerative brain diseases such as Alzheimer's disease (AD) have profound global consequences, including significant health, social, and economic impacts. Rational therapeutic interventions that can effectively address sleep disturbances and memory impairment in people with AD, as well as the complex etiopathogenesis of the disease, remain major unmet clinical needs. The circadian clock represents a new potential therapeutic target for AD, given that its dysfunction may contribute to the development and clinical manifestations of the disease through regulation of sleep, hippocampal function, and neurodegeneration. Moreover, the identification of age-related changes in the circadian regulation of processes underlying memory function in the hippocampus may open new avenues to correct dysregulated rhythms and thereby prevent or reverse cognitive decline. In the first part of this thesis, young and middle-aged non-transgenic mice were compared using quantitative mass spectrometry in order to perform a proteome-wide screen for proteins with rhythmic abundances in the hippocampus and dissect changes in the temporal orchestration of biological pathways during aging. Aging disrupted circadian regulation of the hippocampal proteome and altered the daily expression profiles of proteins implicated in age-related neurodegenerative diseases and hallmarks of aging, suggesting that aging-induced changes in rhythmic physiology may play important roles in cognitive decline and aging-associated brain disorders such as AD. In the second part of this thesis, the therapeutic potential of a small molecule circadian clock modifier (PF-670462) was evaluated in 3xTg-AD mice using mass spectrometry-based proteomic analyses as well as cognitive and behavioural testing. PF-670462 reversed hippocampal proteomic alterations in several AD-related and clock-regulated pathways, rescued working memory deficits, and normalized behavioural circadian rhythm disturbances in 3xTg-AD mice. This study provides in vivo proof of concept for the efficacy of direct circadian clock modulation in a transgenic mouse model of AD. Together, these studies highlight emerging roles for the circadian clock in hippocampal aging and as a therapeutic target for AD.

Sleep and Clocks in Aging and Longevity

2023-03-06 Family & Relationships
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Release : 2023-03-06
Genre : Family & Relationships
Kind : eBook
Book Rating : 68X/5 ( reviews)

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Book Synopsis Sleep and Clocks in Aging and Longevity by : Anita Jagota

Download or read book Sleep and Clocks in Aging and Longevity written by Anita Jagota. This book was released on 2023-03-06. Available in PDF, EPUB and Kindle. Book excerpt: This edited volume focuses on the interplay between sleep and circadian rhythms with health, aging and longevity. Sleep is absolutely important for human health and survival, as insufficient sleep is associated with a plethora of conditions, including the poor quality of life, onset of several diseases, and premature death. The sleep–wake cycle is an evolutionary conserved neurobiological phenomenon, and is a prominent manifestation of the biological clocks localised in the suprachiasmatic nucleus (SCN). Understanding bidirectional relationship between sleep and circadian rhythms is of utmost importance and urgency, especially in the context of modern lifestyle where sleep is often out of phase with the internal body clocks, social jetlag, artificial lights and so on. The 25 chapters by leading researchers and experts from 11 countries are arranged into seven sections: understanding sleep and clock interlink in health and longevity; sleep, aging and longevity; clock, aging and longevity; melatonin, sleep and clock; genetic regulation of sleep and clock; therapeutic interventions in sleep disorders and clock misalignment; and experimental models to study sleep and clocks in aging and longevity. This book is useful for advanced undergraduate and graduate students, and researchers, educators, and other biomedical professionals.

Roles of Sleep Disruption and Circadian Rhythm Alterations on Neurodegeneration and Alzheimer’s Disease

2021-10-22 Science
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Release : 2021-10-22
Genre : Science
Kind : eBook
Book Rating : 388/5 ( reviews)

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Book Synopsis Roles of Sleep Disruption and Circadian Rhythm Alterations on Neurodegeneration and Alzheimer’s Disease by : Marilyn J. Duncan

Download or read book Roles of Sleep Disruption and Circadian Rhythm Alterations on Neurodegeneration and Alzheimer’s Disease written by Marilyn J. Duncan. This book was released on 2021-10-22. Available in PDF, EPUB and Kindle. Book excerpt:

Circadian Clock in Brain Health and Disease

2021-11-13 Medical
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Release : 2021-11-13
Genre : Medical
Kind : eBook
Book Rating : 476/5 ( reviews)

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Book Synopsis Circadian Clock in Brain Health and Disease by : Olivia Engmann

Download or read book Circadian Clock in Brain Health and Disease written by Olivia Engmann. This book was released on 2021-11-13. Available in PDF, EPUB and Kindle. Book excerpt: In this book, leading experts in the field review how circadian rhythms impact the brain. An essential function of mammalian life is the exploitation of the regularities provided by the 24-hour cycle of day and night. The development and evolution of circadian clock mechanisms have allowed us to optimally adapt our behavior and physiology to the external world. Not surprisingly, a growing body of evidence links the disruption of circadian rhythms by genetic, lifestyle and environmental factors to illnesses of the brain. In the first section of the book, readers will learn about the molecular and anatomic architecture of circadian function in mammals. The ways in which environmental disruptions and misalignments can influence such mechanisms and therefore impair brain function and health status are also addressed. In the second part, the focus shifts to those brain regions responsible for brain function and the body-wide regulation of circadian function. Amongst others, special attention is paid to the role of astrocytes and the brain’s reward and hyprocretin / orexin systems. The book concludes with an extensive discussion on the consequences of circadian rhythm dysfunction. Several chapters present the latest findings on Attention Deficit Hyperactivity Disorder, schizophrenia, autism spectrum disorder, drug abuse and mood disorders. Written by auhorities in the field, the book provides a state-of-the-art review of the latest findings on circadian clocks in the brain and highlights their potentially far-reaching impacts on our health and well-being. As such, it is essential reading for all neuroscientists and clinicians seeking to understand the intricate connections between circadian rhythms and brain health and illness.

Circadian Clock and Aging

2024-10-15 Science
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Release : 2024-10-15
Genre : Science
Kind : eBook
Book Rating : 949/5 ( reviews)

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Book Synopsis Circadian Clock and Aging by : Syed Ibrahim Rizvi

Download or read book Circadian Clock and Aging written by Syed Ibrahim Rizvi. This book was released on 2024-10-15. Available in PDF, EPUB and Kindle. Book excerpt: This book aims to understand the inherent circadian cycles of biological processes and their role in maintaining health and healing a variety of diseases. The book is divided into eight sections. The first section introduces circadian rhythms and aging. The second section focuses on the detailed mechanistic approach of oscillatory pathways in mammals. The next section summarizes the sensitivity of the biological clock towards light and the circadian response to melatonin in mammals. The fourth section addresses the circadian architecture at the cellular level and introduces an age-dependent experimental model of rodents for subsequent biochemical and molecular investigations. The subsequent section covers the complexity of circadian regulation in mitochondrial dynamics and its impact on aging. The sixth section of the book discusses the findings obtained from different experimental approaches as a critical threat to the functioning of clock regulatory mechanisms and its associated health consequences during aging in humans and animal models. The circadian oscillatory mechanisms that are dysregulated and might play an important role in the development and progression of neurological disorders such as Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD), and Amyotrophic Lateral Sclerosis (ALS), etc are discussed in the next section. Towards the end, the book explores the circadian clock as a possible drug target to restore circadian oscillations.

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