Alterations in the Neuronal Cytoskeleton in Alzheimer's Disease (Advances in Behavioral Biology) (Vo pdf epub mobi txt 电子书 下载 2026

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出版者:Springer

作者:George Perry

出品人:

页数:240

译者:

出版时间:1988-03-01

价格:USD 138.00

装帧:Hardcover

isbn号码:9780306427664

丛书系列:

图书标签:

• Alzheimer's Disease
• Neuronal Cytoskeleton
• Neuroscience
• Behavioral Biology
• Neuropathology
• Brain
• Neurodegeneration
• Cognitive Decline
• Molecular Biology
• Aging

Alzheimer's Disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline, memory loss, and behavioral changes. While the accumulation of amyloid-beta plaques and tau tangles are hallmarks of AD pathology, mounting evidence points to significant disruptions within the neuronal cytoskeleton as a critical and often overlooked contributor to disease progression and neuronal dysfunction. This volume delves deeply into the intricate and dynamic world of the neuronal cytoskeleton and its profound alterations in the context of Alzheimer's Disease. The neuronal cytoskeleton, a complex network of protein filaments – microtubules, neurofilaments, and actin filaments – acts as the structural scaffold of neurons, essential for maintaining their shape, facilitating intracellular transport, and enabling synaptic plasticity. In healthy neurons, these components are precisely regulated, undergoing dynamic assembly and disassembly to support neuronal function. However, in AD, this delicate balance is severely disrupted. Microtubules, the long, hollow cylinders formed by tubulin subunits, are crucial for axonal transport, the movement of organelles, vesicles, and proteins along the neuron. In AD, tau protein, a microtubule-associated protein, becomes abnormally hyperphosphorylated and aggregates into neurofibrillary tangles (NFTs). This hyperphosphorylation leads to tau detaching from microtubules, causing their destabilization and ultimately, their breakdown. The loss of microtubule integrity cripples axonal transport, leading to the accumulation of cargo in the soma and deficits in the delivery of essential molecules to the synapse. This impaired transport is a major contributor to synaptic dysfunction and neuronal death. This volume explores the specific tau modifications implicated in microtubule destabilization, the role of various kinases and phosphatases in regulating tau phosphorylation in AD, and the direct impact of tau pathology on microtubule dynamics and function. It will examine cutting-edge research employing advanced imaging techniques to visualize these changes in vivo and in post-mortem tissues. Neurofilaments, another major component of the neuronal cytoskeleton, are intermediate filaments that provide structural support to axons and contribute to their diameter, influencing the speed of action potential conduction. In AD, there is evidence of neurofilament dysregulation, including altered expression, assembly, and phosphorylation. These changes can compromise axonal integrity, making them more susceptible to damage and contributing to axonal beading and eventual degeneration. The volume will discuss the current understanding of neurofilament behavior in AD, exploring potential mechanisms for their abnormal accumulation and fragmentation, and the consequences for axonal health and neuronal signaling. It will also touch upon emerging biomarkers associated with neurofilament pathology, which hold promise for early diagnosis and monitoring of disease progression. Actin filaments, the thinnest cytoskeletal elements, are highly dynamic and play critical roles in neuronal morphology, growth cone guidance, and synaptic plasticity, particularly at the postsynaptic density. In AD, actin dynamics are significantly disrupted, impacting dendritic spine structure and function. Dendritic spines are the primary sites of excitatory synaptic input, and their morphology is closely tied to learning and memory. AD-associated pathology, including the presence of amyloid-beta oligomers, can lead to spine loss and alterations in spine shape, directly contributing to cognitive deficits. This volume will investigate the intricate interplay between AD pathology and actin dynamics, focusing on how altered actin polymerization and depolymerization affect spine morphology, synaptic receptor trafficking, and ultimately, synaptic transmission. It will also explore the role of actin-binding proteins in mediating these changes and the potential of targeting actin dynamics as a therapeutic strategy. Beyond these primary cytoskeletal components, the volume will also investigate the crucial cytoskeletal regulatory proteins and their dysregulation in AD. This includes motor proteins like kinesins and dyneins, which are responsible for cargo transport along microtubules, and actin-binding proteins that modulate actin filament dynamics. Understanding how these proteins are affected by AD pathology is essential for comprehending the cascade of events leading to neuronal dysfunction. For instance, the impairment of kinesin and dynein function due to microtubule instability directly exacerbates axonal transport deficits. Furthermore, the volume will explore the interplay between the cytoskeleton and other AD pathologies. The relationship between amyloid-beta and tau pathology and their collective impact on the cytoskeleton is a complex and active area of research. Amyloid-beta oligomers have been shown to directly interact with cytoskeletal components and trigger downstream events that lead to tau hyperphosphorylation and cytoskeletal breakdown. Conversely, cytoskeletal disruptions may facilitate the spread of tau pathology. This volume will dedicate chapters to unraveling these complex interactions and the consequences for neuronal integrity. The volume will also address the therapeutic implications of targeting cytoskeletal alterations in AD. Strategies aimed at stabilizing microtubules, restoring axonal transport, promoting spine resilience, or modulating actin dynamics represent promising avenues for future treatment. This includes exploring the potential of pharmacological agents that promote tau detachment from microtubules without causing their complete disassembly, or molecules that can enhance the function of motor proteins. The challenges and opportunities in developing such targeted therapies will be a significant focus. Methodologies and advanced techniques used to study cytoskeletal alterations in AD will be comprehensively reviewed. This includes advanced microscopy techniques such as super-resolution microscopy and cryo-electron microscopy, which allow for unprecedented visualization of cytoskeletal structures and their interactions with AD-related proteins. Furthermore, biochemical assays and genetic models will be discussed for their role in dissecting the molecular mechanisms underlying cytoskeletal dysregulation. This volume is intended for neuroscientists, molecular biologists, neurologists, and researchers working in the fields of neurodegenerative diseases, molecular neuroscience, and cell biology. It provides a comprehensive and up-to-date overview of the current state of knowledge regarding cytoskeletal alterations in Alzheimer's Disease, highlighting key findings, emerging trends, and future research directions. By synthesizing the latest research, this volume aims to foster a deeper understanding of the critical role of the neuronal cytoskeleton in AD pathogenesis and to inspire the development of novel therapeutic strategies for this debilitating disease. It will serve as an invaluable resource for anyone seeking to understand the molecular underpinnings of neuronal dysfunction in Alzheimer's Disease, with a particular emphasis on the often-underestimated but vital contributions of the neuronal cytoskeleton. The detailed exploration of these fundamental cellular structures and their pathological transformation in AD will offer new perspectives on disease mechanisms and potential intervention points.

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