Apoptosis in Neurobiology: Concepts and Methods doc

[...]... Carolina © 1999 by CRC Press LLC Section A Diseases and Concepts © 1999 by CRC Press LLC 1 Introduction: Occurrence, Mechanisms, and Role of Apoptosis in Neurobiology and in Neurologic Disorders Rose-Mary Boustany and Yusuf A Hannun CONTENTS 1.1 Molecular Mechanisms of Apoptosis 1.2 Mechanisms of Apoptosis in Neurological Disorders 1.3 Methodologies in Apoptosis References Apoptosis in the developing... Fas–Fas-L interactions,14 ceramide as proapoptotic lipid second messenger and the sphingomyelin cycle15; the neuroprotective bcl-2 oncogene and its homologues,16 p53 and retinoblastoma genes as inducers of growth arrest and apoptosis1 7; the early initiator and later executionary caspase cascades and their triggers and inhibitors18; the role of the mitochondrion as central processor of incoming messages, and. .. fodrin, protein kinases, and other structural or regulatory proteins This process culminates in the organized collapse of the nucleus, membranes, and cellular organelles Many neuronal proteins are now recognized as substrates of caspases, including presenilins and huntingtin.23,24 The orderly breakdown of dying cells through the apoptotic mechanisms results in the packaging of cellular debris into apoptotic... neuraxis and for one discrete set of cells, apoptosis is heterogeneous in mechanism Moreover, apoptotic cell death involves not only projection neurons innervating skeletal muscle and sensory neurons of the dorsal root © 1999 by CRC Press LLC ganglia, but also supporting glial cell elements in the spinal cord and peripheral nerves and interneurons intrinsic to the spinal cord.9-12 3.2.2 Midbrain, Forebrain,... generated early in the development of the neocortex are situated in this zone beneath the main cortical plate Subplate neurons interconnect with the neurons in layer I and participate in important cell–cell interactions with migrating neurons and with incoming afferent and efferent projections This structure is particularly prominent in human and primate brain Its disappearance during the course of... neuronal or photoreceptor death in the brain and eye, but remains phenotypically silent in other tissues 1.3 Methodologies in Apoptosis A long list of techniques exists that facilitates the study of apoptosis in neurobiology and other disciplines The second part of this book covers many techniques that the authors have found useful These include TUNEL staining and other staining techniques that capitalize... stages of spinal cord development and continues throughout the later stages Of interest is the finding that early apoptotic death of spinal motoneurons may be determined by intrinsic programs or local factors within the spinal cord, whereas later stages of motoneuron apoptotic death may be dominated by trophic factor in uence related to interactions and innervation of target muscles.9 Thus, even in this... defects in the survival motor neuron (SMN) or neuronal apoptosis inhibitory protein (NAIP) defective in spinal muscular atrophy.5-7 Alternatively, neurodegenerative disorders can result from defects in dominant genes, as seen in the expanded triplet repeat diseases These represent a deleterious gain of function model where the expanded CAG/polyglutamine tract in the mutant protein results in novel... carefully orchestrated and effective apoptosis in the developing fetus can have serious and long-lasting effects in the adult Congenital brain malformations such as heterotopias, schizencephaly, myelomeningocoele, and many others probably represent poorly designed and/ or incomplete apoptosis An accelerated rate of apoptosis is purposefully induced when cancers are treated with radiation and various chemotherapeutic... is known precisely which cells in the developing organism (and at what point in their lineage) are destined to die, this being one of the terminally differentiated states In C elegans, there are regional differences in the patterns of programmed cell death, and cell death appears to function primarily to generate regional diversity,1 perhaps by eliminating certain sublineages.4 Genetic studies have . Diseases and Concepts 1. Introduction: Occurrence, Mechanisms, and Role of Apoptosis in Neurobiology and in Neurologic Disorders R M. Boustany and Y. A. Hannun 2. Cell Death in the Developing. he recieved training in internal medicine. He then trained in hematology and medical oncology at Duke University. He also trained in biochemistry with Dr. Robert Bell. He then joined the faculty of. in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage or retrieval system, without prior permission in writing