Role of Proteases in the Pathophysiology of Neurodegenerative Diseases

Researchers seeking problems that offer more hope of success often avoid subjects that seem to be difficult to approach experimentally, or subjects for which experimental results are difficult to interpret. The breakdown part of protein turnover in vivo, particularly in nervous tissue, was such a subject in the past – it was difficult to measure and difficult to explore the mechanisms involved. For factors that influence protein metabolism, it was thought that protein content, function, and distribution are controlled only by the synthetic mechanisms that can supply the needed specificity and response to stimuli. The role of breakdown was thought to be only a general metabolic digestion, elimination of excess polypeptides. We now know that the role of breakdown is much more complex: it has multiple functions, it is coupled to turnover, and it can affect protein composition, function, and synthesis. In addition to eliminating abnormal proteins, breakdown has many modulatory functions: it serves to activate and inactivate enzymes, modulate membrane function, alter receptor channel properties, affect transcription and cell cycle, form active peptides, and much more. The hydrolysis of peptide bonds often involves multiple steps, many enzymes, and cycles (such as ubiquination), and often requires the activity of enzyme complexes. Their activation, modification, and inactivation can thus play an important role in biological functions, with numerous families of proteases participating. The specific role of each remains to be elucidated.

Science & Math

Lacy, Charles F.

Howie, Alexander J.

Goldman, Morton P.

Lance, Leonard L.

FRIEDMAN, HERMAN

Weisman

Katz, Lynda J.

Goldstein, Gerald

Beers, Sue R.

Young, David B.

Honeyman, Allen

Lajtha, Able

Bendinelli, Mauro

Newland, Robert

Biological Sciences

Springer

Role of Potassium in Preventive Cardiovascular Medicine: Information related to this question has accumulated for nearly a hundred years, from work in cellular physiology, experimental studies in animals, clinical trials, and from population and epidemiological investigations. Because of the importance of integration of this diverse body of information, the most significant findings are brought together in this book. This body of information provides emphatic support for the importance of high dietary potassium intake as a means of reducing the risk of cardiovascular diseases, as it provides abundant evidence that potassium depletion has significant, deleterious influences that increase the risk of hypertension, atherosclerosis, heart failure, and stroke. At this time we have the results and data required to strongly recommend dietary modification to increase potassium intake. But making the recommendation will only be the first step; convincing the population to undertake the change in eating patterns will be challenging, and will require concerted actions by government, the medical community, and the food and beverage industries. The outcome promises to be well worth the investment. `This book is an excellent source of current information on the many roles of potassium in cardiovascular disease. It succinctly mixes basic physiology and clinical aspects in a manner that will make it of great value to both researchers and clinicians.' Norman M. Kaplan, M.D., Professor of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX

Role of Potassium in Preventive Cardiovascular Medicine

Although cardiac output is measured as the flow of blood from the left ventricle into the aorta, the system that controls cardiac output includes many other components besides the heart itself. The heart's rate of output cannot exceed the rate of venous return to it, and therefore, the factors governing venous return are primarily responsible for control of output from the heart. Venous return is affected by its pressure gradient and resistance to flow throughout the vascular system. The pressure gradient for venous return is a function of several factors including the blood volume flowing through the system, the unstressed vascular volume of the circulatory system, its capacitance, mean systemic pressure, and right atrial pressure. Resistance to venous return is the sum of total vascular resistance from the aortic valve to the right atrium. The sympathetic nervous system and vasoactive circulating hormones affect short-term resistance, whereas local tissue blood flow autoregulatory mechanisms are the dominant determinants of long-term resistance to venous return. The strength of contraction of the heart responds to changes in atrial pressure driven by changes in venous return, with small changes in atrial pressure eliciting large changes in strength of contraction, as described by the Frank-Starling mechanism. In addition, the autonomic nervous system input to the heart alters myocardial pumping ability in response to cardiovascular challenges. The function of the cardiovascular system is strongly affected by the operation of the renal sodium excretion-body fluid volume-arterial pressure negative feedback system that maintains arterial blood pressure at a controlled value over long periods. The intent of this volume is to integrate the basic knowledge of these cardiovascular system components into an understanding of cardiac output regulation.

Control of Cardiac Output (Colloquium Series on the Cell Biology of Medicine)

Morgan & Claypool Life Sciences

Several physiological mechanisms act to regulate renal potassium excretion and distribution. Together they comprise an integrated control system that may be envisioned as being made up of several interacting negative feedback control mechanisms, all affecting removal of potassium from the extracellular fluid by renal excretion or transfer across cell membranes into or out of the intracellular compartment. The intent of this presentation is to describe the mechanisms of potassium regulation, beginning in Chapter 1 with an overview of the system, Chapter 2 with mechanisms that determine movement of potassium between the extracellular and intracellular compartments, in Chapter 3 focusing on renal tubular transport systems, and in Chapter 4 presenting the mechanisms of control of aldosterone secretion. Greatest emphasis will be on describing the integrated functions of the components, in Chapter 5, as they operate together in a system to regulate extracellular potassium concentration in response to commonly encountered challenges. In addition, interactions between potassium regulation and commonly used medications will be considered in Chapter 6, and in Chapter 7 the causes and treatment of dysregulation of potassium will be discussed. Table of Contents: Preface / Introduction / Regulaton of Potassium Distribution / Potassium Transport in Segments of the Nephron / Regulation of Potassium Excretion / Control of Aldosterone Secretion / System Analysis of Potassium Regulation / Pharmacotherapeutics Interactions / Disorders of Potassium Control / References / Author Biography

Control of Potassium: Distribution, Excretion, and Extracellular Concentration (Colloquium Integrated Systems Physiology: From Molecule to Function to Disease)

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