# CELL BIOLOGY OF A NEUROTROPHIC PROTEIN FROM GLIAL CELLS

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 1992 · $146,160

## Abstract

The long term goal is to increase understanding of molecular mechanisms
involved in development and maintenance of the nervous system, and how
perturbations of these processes might be involved in certain disease
states, especially inherited diseases and age-related disorders.  The focus
of the research is on S100beta, a glial cell protein that has neurotrophic
activity; i.e., S100beta can selectively stimulate neurite outgrowth and
enhance survival of CNS neurons.  Feasibility data indicate that S100beta
also stimulates glial cell proliferation.  Thus, S100beta may be involved
in the coordinate development and maintenance of the CNS by synchronously
stimulating the differentiation of neurons and the proliferation of glia.
However, nothing is known about the mechanisms which enable these cell
types to respond differentially to S100beta.  It is the goal of this
proposal to fill a void in our knowledge of the molecular mechanisms by
which S100beta stimulates glial cell proliferation.  The two questions
being addressed are:  1. what are the characteristics of the cell surface
components that recognize S100beta; i.e. the receptor?  and 2. how does
binding of S100beta bring about stimulation of cell proliferation; i.e.,
signal transduction pathways?  By addressing these two mechanistically
coupled questions, insight will be gained into how molecular recognition of
S100beta by the glial cell is transduced through intracellular signal
transduction events to the eventual proliferative response.  These studies
will provide the necessary knowledge to pursue longer-term studies aimed at
probing molecular mechanisms at a more detailed level, in order to
understand how the cell surface events are coupled mechanistically to the
nuclear events (changes in gene expression) and vice versa, and what
distinguishing features of these pathways determine the specific biological
responses of glial vs neuronal cells to S100beta stimulation.  This
research also has the potential to increase understanding of the
neuropathologies associated with age-related disorders such as Down
syndrome and Alzheimer's disease.  Clearly, because S100beta can affect
both glial and neuronal cells, aberrant S100beta gene expression and
protein production/targeting during critical periods of development could
have profound effects on nervous system function.  In this regard, the
abnormally high levels of S100beta found in the brains of patients with
these diseases may be linked directly to the observed gliosis and abnormal
neuritic outgrowth, and to the cascade of neuropathological events that
with aging lead to mental retardation and dementia.  This research has the
potential to provide the basic knowledge necessary for future approaches to
diagnostics and therapeutics for these age-related disorders.

## Key facts

- **NIH application ID:** 3123124
- **Project number:** 1R01AG011138-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **SAM.gov UEI:** GTNBNWXJ12D5
- **Principal Investigator:** LINDA J VAN ELDIK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $146,160
- **Award type:** 1
- **Project period:** 1992-05-15 → 1995-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123124

## Citation

> US National Institutes of Health, RePORTER application 3123124, CELL BIOLOGY OF A NEUROTROPHIC PROTEIN FROM GLIAL CELLS (1R01AG011138-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123124. Licensed CC0.

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