MOLECULAR STUDY ON MYELIN-ASSOCIATED NEURAMINIDASE

Project: Research project

Project Details

Description

DESCRIPTION: (adapted from Applicant's Abstract) Although a growing
body of evidence has suggested that sialoglycoconjugates may play an
important role in the formation and maintenance of the myelin sheath,
information about their metabolism and regulation in myelin and
oligodendroglial cells is still scanty. The investigators have
studied neuraminidase activities in the central nervous system and
demonstrated the presence of neuraminidase activities intrinsic to
myelin and oligodendroglial cells. To elucidate the functional roles
of neuraminidase in myelin and oligodendroglial cells, the following
specific aims are proposed: (1) purification and characterization of
myelin-associated neuraminidase, (2) localization of the enzyme, (3)
regulatory mechanisms for developmental expression of the enzyme
activities in myelin and oligodendroglial cells, and (4) functional
roles of myelin-associated neuraminidase. To achieve these goals, the
investigators will first purify myelin-associated neuraminidase to
homogeneity from rat brain. The biochemical and kinetic properties
of the enzyme will be examined and compared with those of
neuraminidase activities in microsomes. Specific antibodies against
the enzyme will be prepared to examine the localization of the enzyme
using immunocytochemical and immunoblotting techniques. In order to
examine whether the neuraminidase activities in myelin and
oligodendroglial cells are regulated at the mRNA level, the
developmental expression of mRNA coding for myelin-associated
neuraminidase will be examined using a specific cDNA probe prepared
with mRNA of rat oligodendroglial cells.The mechanism of the
developmental changes in the activity of the myelin enzyme will also
be investigated by analyzing the amounts, integrity, and micro-
environment of the enzyme during development. To examine the
metabolic role of myelin-associated neuraminidase, developmental
changes in the composition of sialoglycoconjugates in myelin and
oligodendroglial cells will be examined in relation to the
neuraminidase activities directed toward endogenous
sialoglycoconjugates as well as exogenous substrates.The possibility
that myelin-associated neuraminidase may function as an adhesion
molecule will be investigated using different types of binding
experiments and cell culture systems. The achievement of these
specific aims should provide vital information concerning the role of
myelin-associated neuraminidase in the formation and maintenance of
the myelin sheath.
StatusNot started

Funding

  • National Institute of Neurological Disorders and Stroke

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