SPHINGOGLYCOLIPIDS IN NORMAL AND PATHOLOGICAL BRAINS

Project: Research project

Description

The major objectives of this project are to study the distribution,
structure, metabolism, and function of glycosphingolipids (GSLs),
particularly gangliosides, in normal and pathological tissues, cells and
subcellular organelles of the CNS. We will engage in the isolation and
characterization of new GSLs and in the elucidation of new biosynthetic
pathways. We will develop new methodologies for investigating their
subcellular localization and turnover, and for their chemical synthesis.
We will also develop new strategies for elucidating their primary and
secondary structures and relate this information to their functional role
in biological membranes. The relationship between myelin and
oligodendroglia will be examined through the metabolism of components that
are intrinsic to these two compartments during brain development. Special
emphasis will be placed on the functional role of myelin lipid-protein
interactions in myelination and the maintenance of myelin membrane
integrity. The mode of myelin lipid-protein interaction will be
investigated by such physical techniques as nuclear magnetic resonance
spectrometry and differential scanning calorimetry. This knowledge is
essential in understanding the physiological role of myelin-associated
neuraminidase and the regulation of proteolysis of myelin basic protein
myelination and demyelination. Finally, we will investigate the
pathogenesis of slow virus agents by studying the composition and
metabolism of membrane ganglioside in scrapie mouse brains. We also plan
to investigate the expression of gangliosides in a variety of neurological
diseases and in an animal model which exhibit astrocytosis in order to
better understand the relationship between abnormal ganglioside metabolism
and physiological dysfunction in these neurological disorders.
StatusFinished
Effective start/end date6/1/788/31/12

Funding

  • National Institutes of Health: $346,716.00
  • National Institutes of Health
  • National Institutes of Health: $25,000.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $369,964.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $50,000.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $339,625.00
  • National Institutes of Health: $335,968.00
  • National Institutes of Health: $356,424.00
  • National Institutes of Health: $322,026.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $13,870.00
  • National Institutes of Health
  • National Institutes of Health: $339,625.00
  • National Institutes of Health: $339,625.00
  • National Institutes of Health: $331,644.00
  • National Institutes of Health: $361,250.00

Fingerprint

Gangliosides
Glycosphingolipids
Brain
Myelin Sheath
Nervous System
Glycosyltransferases
Nervous System Diseases
Sialyltransferases
Intellectual Disability
Embryonic Stem Cells
Enzymes
Genes
Glycosylation
Cell Differentiation
Myelin Proteins
Lipids
(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase
Scrapie
Membranes
Phosphorylation

ASJC

  • Medicine(all)
  • Neuroscience(all)