Protein Homeostasis Diseases


Book Description

Protein Homeostasis Diseases: Mechanisms and Novel Therapies offers an interdisciplinary examination of the fundamental aspects, biochemistry and molecular biology of protein homeostasis disease, including the use of natural and pharmacological small molecules to treat common and rare protein homeostasis disorders. Contributions from international experts discuss the biochemical and genetic components of protein homeostasis disorders, the mechanisms by which genetic variants may cause loss-of-function and gain-of-toxic-function, and how natural ligands can restore protein function and homeostasis in genetic diseases. Applied chapters provide guidance on employing high throughput sequencing and screening methodologies to develop pharmacological chaperones and repurpose approved drugs to treat protein homeostasis disorders. - Provides an interdisciplinary examination of protein homeostasis disorders, with an emphasis on treatment strategies employing small natural and pharmacological ligands - Offers applied approaches in employing high throughput sequencing and screening to develop pharmacological chaperones to treat protein homeostasis disease - Gathers expertise from a range of international chapter authors who work across various biological methods and disease specific disciplines of relevance




Protein Homeostasis, Second Edition


Book Description

The entire life cycle of a protein-from synthesis and folding to transport and degradation-is carefully controlled by the proteostasis network. This network, consisting of many interconnected pathways and processes, manages protein homeostasis by dynamically responding to the needs of the cell. Stress and aging can challenge the proteostasis network, resulting in the aggregation of misfolded proteins-a feature of numerous neurodegenerative conditions. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology provides a comprehensive update on how the proteostasis network functions in healthy cells and the diseases that result when protein quality control goes awry. The contributors examine the relevant biochemical attributes of proteins (e.g., solubility), the functions of normal protein aggregates (e.g., biofilm formation in bacteria), and the various heat shock proteins, chaperones, translocation machineries, proteasomes, signaling factors, and transcriptional programs involved in proteostasis. The roles of specific subcellular structures-the endoplasmic reticulum, mitochondria, ribosomes, lysosomes, and cytoplasm-in protein quality control are covered, as is the regulation of proteostasis at the organismal level (e.g., via neuronal activity). Discussions of the responses by cells when errors in protein quality control occur, the medical disorders that can result (e.g., Alzheimer disease), and pharmacologic approaches to ameliorate protein conformational disorders are also included. This book is therefore an essential reference for biochemists, cell biologists, and all biomedical scientists wishing to understand the pathological consequences of and potential therapies for proteostasis deficiencies in common human diseases.




Protein Homeostasis


Book Description

Proper folding of proteins is crucial for cell function. Chaperones and enzymes that post-translationally modify newly synthesized proteins help ensure that proteins fold correctly, and the unfolded protein response functions as a homeostatic mechanism that removes misfolded proteins when cells are stressed. This book covers the entire spectrum of proteostasis in healthy cells and the diseases that result when control of protein production, protein folding, and protein degradation goes awry.




Functions and Mechanisms of Bacterial Protein Homeostasis and Stress Responses


Book Description

The Cover Image for This Research Topic is Used With Permission of the Authors and Publishers of the Following Article: Winkler J, Seybert A, König L, Pruggnaller S, Haselmann U, Sourjik V, Weiss M, Frangakis AS, Mogk A, Bukau B.EMBO J. 2010 Mar 3;29(5):910-23. doi: 10.1038/emboj.2009.412. Epub 2010 Jan 21




Protein Metabolism and Homeostasis in Aging


Book Description

Aging is loosely defined as the accumulation of changes in an organism over time. At the cellular level such changes are distinct and multidimensional: DNA replication ceases, cells stop dividing, they become senescent and eventually die. DNA metabolism and chromosomal maintenance, together with protein metabolism are critical in the aging process. The focus of this book is on the role of protein metabolism and homeostasis in aging. An overview is provided of the current knowledge in the area, including protein synthesis, accuracy and repair, post-translational modifications, degradation and turnover, and how they define and influence aging. The chapters mainly focus on well-characterised factors and pathways, but new areas are also presented, where associations with aging are just being elucidated by current experimental data. Protein turnover, the balance between protein synthesis and protein degradation are carefully maintained in healthy cells. Chapters 1 and 2 illustrate that aging cells are characterised by alterations in the rate, level and accuracy of protein synthesis compared to young ones, and that mRNA translation, essential for cell growth and survival, is controlled at multiple levels. The theory that growth and somatic maintenance are believed to be antagonistic processes is described in Chapter 3: inhibition of protein synthesis results in decreased rates of growth and development, but also confers an extension of lifespan, as shown for example by the effects of dietary restriction in various models organisms.




Anatomy and Physiology


Book Description







Protein Homeostasis in Drug Discovery


Book Description

Protein Homeostasis in Drug Discovery Comprehensive resource on all aspects of protein homeostasis, covering both historical perspectives and emerging technologies that are revolutionizing the field Protein Homeostasis in Drug Discovery highlights drug discovery and development efforts targeting protein homeostasis and considers the emerging appreciation that a protein’s activity may not be the only factor to consider when developing therapeutic agents. The chapters cover various aspects of protein homeostasis such as cellular localization, abundance, interactions, and more. Moreover, the text contains up-to-date information regarding targeted protein degradation, an emerging drug discovery modality. Readers interested in targeting different regulatory events that control protein homeostasis or modulating protein abundance will find this book an excellent resource. Furthermore, those interested in the link between biological function and regulating protein levels in living organisms, especially in the context of drug discovery, will learn from numerous examples discussed in this book. In Protein Homeostasis in Drug Discovery, readers can expect to find information on: Protein folding, quality control, pharmacology, and drug targeting processes Recent advances in our understanding of protein homeostasis, covering emerging technologies and opportunities for therapeutic intervention Targeted protein degradation (TPD) and strategies such as PROTACs and molecular glues, including a chapter on TPD as an antiviral drug discovery strategy Drug discovery and development efforts aimed at correcting, stabilizing, and rescuing proteins, with examples included Advantages and key shortcomings of both phenotypic and target-based traditional drug discovery methods Collectively, Protein Homeostasis in Drug Discovery offers the reader an opportunity to learn more about the importance of considering and targeting protein homeostasis. The text is a must-read resource for academics, professionals in the pharmaceutical industry, and advanced students in various science-related fields.







Immunity, Tumors and Aging: The Role of HSP70


Book Description

The book is dedicated to the topical area of biology and medicine and the role of stress proteins HSP70 in the regulation of intracellular protein homeostasis, signaling transduction and cell protection. The book is divided into chapters, which describe the discovery of HSP70 and its molecular structure, the mechanism of the synthesis and function in normal and damaged cells, examine the role of HSP70 in immunity, cancerogenesis, aging, Alzheimer's disease and cardiac surgery. In this book, the author looks at HSP70 as a factor which prevents the transformation of homeostasis mechanisms of intracellular proteins into a link in the pathogenesis of a disease.