TY - JOUR
T1 - A cellular approach to neurological disease
AU - McKhann, G. M.
PY - 1978/12/1
Y1 - 1978/12/1
N2 - The brain is a highly complex organ, with a marked heterogeneity of cell type. Thus, biochemical studies of whole tissue reflect the composition and metabolism of a mixture of specific cells, subcellular membranes and organelles. The authors have attempted to overcome these difficulties by isolating purified populations of specific cell types from brain. These purified populations can be maintained in vitro and used for studies of cell-specific metabolic processes. For example, oligodendroglia, the cells which make myelin in the central nervous system, can be isolated and maintained. These maintained cells will synthesize lipids which are enriched in myelin and will produce membranous whorls with many of the characteristics of myelin. An alternative approach is to utilize the knowledge of composition of a specific membrane. In the case of myelin, they are studying the enzymes involved in the synthesis of lipids enriched in myelin and other proteins which are constituents of the myelin membrane. Studies of the lipid-synthesizing enzymes are directed toward determining the cellular events taking place during normal and abnormal development. Those of structural proteins are aimed not only at the process of myelination, but also at the process of myelin maintenance. As myelin breaks down, components are released into cerebrospinal fluid. These components can be detected by sensitive assays. A radioimmunoassay for myelin basic protein has been developed and used to detect myelin breakdown in patients with multiple sclerosis. Studies to date indicate that patients with multiple sclerosis undergoing active attacks release myelin basic protein into their cerebrospinal fluid. In contrast, patients with inactive multiple sclerosis do not have demonstrable quantities of this protein. Thus, knowledge of the specific composition of myelin has led to the development of a biochemical test of the activity of demyelinative disease.
AB - The brain is a highly complex organ, with a marked heterogeneity of cell type. Thus, biochemical studies of whole tissue reflect the composition and metabolism of a mixture of specific cells, subcellular membranes and organelles. The authors have attempted to overcome these difficulties by isolating purified populations of specific cell types from brain. These purified populations can be maintained in vitro and used for studies of cell-specific metabolic processes. For example, oligodendroglia, the cells which make myelin in the central nervous system, can be isolated and maintained. These maintained cells will synthesize lipids which are enriched in myelin and will produce membranous whorls with many of the characteristics of myelin. An alternative approach is to utilize the knowledge of composition of a specific membrane. In the case of myelin, they are studying the enzymes involved in the synthesis of lipids enriched in myelin and other proteins which are constituents of the myelin membrane. Studies of the lipid-synthesizing enzymes are directed toward determining the cellular events taking place during normal and abnormal development. Those of structural proteins are aimed not only at the process of myelination, but also at the process of myelin maintenance. As myelin breaks down, components are released into cerebrospinal fluid. These components can be detected by sensitive assays. A radioimmunoassay for myelin basic protein has been developed and used to detect myelin breakdown in patients with multiple sclerosis. Studies to date indicate that patients with multiple sclerosis undergoing active attacks release myelin basic protein into their cerebrospinal fluid. In contrast, patients with inactive multiple sclerosis do not have demonstrable quantities of this protein. Thus, knowledge of the specific composition of myelin has led to the development of a biochemical test of the activity of demyelinative disease.
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M3 - Review article
C2 - 355697
AN - SCOPUS:0018171138
SN - 0021-7263
VL - 143
SP - 48
EP - 57
JO - Johns Hopkins Medical Journal
JF - Johns Hopkins Medical Journal
IS - 2
ER -