Presenilins and Alzheimer's Disease

ISBN-13: 9783642721052 / Angielski / Miękka / 2012 / 100 str.

Steven G. Younkin; Rudolph E. Tanzi

Opis

Molecular and biochemical studies of Alzheimer's disease have recently under gone a major revolution with the discovery of the presenilin genes. Since 1995 when these genes were first identified to carry defects responsible for up to half of early onset familial Alzheimer's disease cases (Sherrington et al. 1995; Levy-Lahad et al. 1995), over 50 Alzheimer-associated mutations have been found in the prese nilin genes, PSI and PS2 (reviewed in Tanzi et al. 1996). Over 200 papers have been published regarding the characterization of the presenilins. Not since the amyloid protein Precursor (APP) was isolated in 1987 (Kang et al. 1987; Goldga ber et al. 1987; Robakis et al. 1987; Tanzi et al. 1987) has the discovery of novel genes had such an impact on the field of Alzheimer's disease research. To whit, five separate sessions at the 1997 Society for Neuroscience Meeting are devoted solely to studies of the presenilins. The presenilins genes have clearly taken the field of Alzheimer's disease research by storm and appropriately so since defects in these genes can cause Alzheimer's disease as early as in one's late twenties. One of the greatest revelations to arise from molecular studies of the preseni lins is the finding that, like the familial Alzheimer's disease mutations in APP, the mutations in the presenilin genes lead to increased production and secretion of the longer form of the A peptide, A 42 (Scheuner et al."

Spis treści

Molecular Genetics of the Presenilins in Alzheimer’s Disease.- Alzheimer’s Disease: A Matter of Dominance.- Alternative Endoproteolysis of the Presenilins and Familial Alzheimer’s Disease.- The APP and PS1/2 Mutations Linked to Early Onset Familial Alzheimer’s Disease Increase the Extracellular Concentration of A?1-42(43).- Metabolism and Function of Presenilin 1.- Mechanistic Studies of the Effect of Presenilins 1 and 2 on APP Metabolism.- Presenilin 2 — APP Interactions.- The Cellular Biology of Presenilin Proteins and a Novel Mechanism of Amyloid ?-Peptide Generation.- Regulation of Presenilin 1 Phosphorylation and Transcriptional Activation of Signal Transduction-Induced Genes by Muscarinic Receptors.- Neuronal Regulation of Presenilin-1 Processing.- Transgenic Approaches to the Study of Alzheimer’s Disease.

O autorze

Molecular and biochemical studies of Alzheimer's disease have recently undergone a major revolution with the discovery of the presenilin genes. An understanding of the mechanisms by which mutations in the presenilin genes cause neurodegeneration and dementia should greatly facilitate the development of novel strategies for treating Alzheimer's disease and related disorders.

Blurb

The discovery in 1995 that defects in the novel presenilin genes harbor defects which cause up to half of all cases of early onset familial Alzheimer's disease cases has rapidly led to the creation of a new and exciting sub-field in Alzheimer's disease research. This has clearly been evidenced by the fact that over 250 papers have now been published regarding the presenilins since their identification in 1995. One of the earliest findings regarding the role of the presenilins in Alzheimer's disease was the discovery that like familial Alzheimer's disease mutations in the amyloid ß protein precursor gene, those in the presenilins lead to dramatically increased production of ß-amyloid in the brains of AD patients. Additionally, the presenilins appear to play roles in programmed cell death (apoptosis) and in CNS development. The provocative chapters in this book written by some of the most highly respected experts in the area of Alzheimer's disease research present some of the latest information concerning the biological function of the presenilins and how defects in these genes cause Alzheimer's disease. The knowledge contained in this volume should help to accelerate ongoing attempts to develop novel treatments for Alzheimer's disease and related disorders.