Proteases And Protease Inhibitors In Alzheimers Disease Pathogenesis

These 22 papers cover protein trafficking, lysosomal proteolysis, calpains, serpins, processing of cytoskeletal proteins, and complex proteolytic cascades of the circulatory system.

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Accumulation and deposition of the amyloid beta-protein (A[beta]) is an invariant feature of Alzheimer's disease (AD). Biochemical, cell biological, animal modeling, genetic, and emerging clinical data all suggest that A[beta] is an upstream initiator of the disease process and its neuropathology. Decreasing brain A[beta] is an emerging therapeutic approach for AD, and currently efforts are being made to block A[beta] production or enhance its clearance through vaccination. A less well understood mechanism of A[beta] clearance is enzymatic degradation by proteases within the brain. The purpose of this thesis is to describe pathways of A[beta] catabolism that may shed light on disease pathogenesis. Further, such insight may prove useful for assessing disease risk as well as offering preventative and therapeutic measures against the disease. I first present evidence that an enzyme genetically associated with AD, the angiotensin-converting enzyme (ACE), is an A[beta]-degrading protease. I determine that ACE is expressed within the brain, and that cellular overexpression of ACE promotes the degradation of A[beta].

This book highlights the pathophysiological complexities of the mechanisms and factors that are likely to be involved in a range of neuroinflammatory and neurodegenerative diseases including Alzheimer's disease, other Dementia, Parkinson Diseases and Multiple Sclerosis. The spectrum of diverse factors involved in neurodegeneration, such as protein aggregation, oxidative stress, caspases and secretase, regulators, cholesterol, zinc, microglia, astrocytes, oligodendrocytes, etc, have been discussed in the context of disease progression. In addition, novel approaches to therapeutic interventions have also been presented. It is hoped that students, scientists and clinicians shall find this very informative book immensely useful and thought-provoking.

Alzheimer's Disease is an ever present problem affecting millions of people around the world and, as people's average lifespan lengthens, its prevalence is set to increase. A global effort is needed to combat the disease, including research to investigate the causes, development of effective treatments and, ultimately, prevention of the disease. Published every two years, these timely books discuss the very latest research. This new volume provides a unique source of reference to the important work being done in this field, it gives academics and clinicians an opportunity to learn about cutting edge developments and covers all aspects of Alzheimer's Disease, including diagnosis, clinical course, epidemiological course and therapeutics and disease mechanisms. Alzheimer's Disease: Advances in Etiology, Pathogenesis and Therapeutics will provide essential information for basic and clinical researchers in Alzheimer's Disease and other dementias as well as for those who care for patients.

Completely updated for its Fourth Edition, this book is the most comprehensive, current review of the molecular and genetic basis of neurologic and psychiatric diseases. More than 120 leading experts provide a fresh, new assessment of recent molecular, genetic, and genomic advances, offer new insights into disease pathogenesis, describe the newest available therapies, and explore promising areas of therapeutic development. This edition features an updated section on psychiatric disease and expanded, updated chapters on human genomics, gene therapy, and ethical issues. Six new chapters cover congenital myasthenic syndromes, hereditary spastic paraplegia, ion channel disorders, the phakomatoses, beta-galactosidase deficiency, and prion diseases. A Neurologic Gene Map describes the chromosome locus of all the genetic diseases and their gene product where known. The fully searchable online text will be available on a companion Website. (www.rosenbergneuroandpsychdisease.com)