# AGING & NEURONAL DEATH--FIRST GENERATION OF NGF ANALOG

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1991 · $96,809

## Abstract

One of the primary pathological processses occurring in the aging
nervous system is neuronal death.  For example, in Alzheimer's disease
(AD) cholinergic neurons in the basal forebrain, which are thought to
function in memory and learning, are lost.  Neurotrophic factors are
proteins which interact with cell surface receptors to promote the
survival and growth of neurons.  There is considerable evidence that
neurotrophic factors such as nerve growth factor (NGF) can prevent
neuronal death or damage and that they may be able to enhance the
function of compromised neurons.  Basal forebrain cholinergic neurons
have NGF receptors and respond to NGF; therefore, NGF may be relevant to
understanding and perhaps minimizing the loss of neurons in AD.  A
significant limitation to both understanding the physiological role of
endogenous NGF in vivo and the potential therapeutic application of NGF
is the lack of stable, low molecular weight agonists and antagonists of
NGF which can effectively reach the central nervous system and penetrate
the brain parenchyma.  The long term objectives of this work are: i) to
begin to define structural features of NGF (NGF's active site) which
will allow it to interact with its receptor and ii) to develop a first
generation of low molecular weight synthetic NGF peptide analogs which
can mimic or inhibit the neurotrophic effect of NGF in vitro and
eventually in vivo.  The general strategy of this proposal is to map the
active site(s) of NGF by synthesizing short peptides corresponding to
potential active sites.  These peptides will be assayed for their
ability to block or mimic several measures of NGF bioactivity in vitro.
By systematically varying which residues of NGF are includes in each
peptide and by making peptides of different lengths, one can begin to
map an active site.  Active peptides will then be modified by
conventional techniques to form a first generation of NGF analogs.  This
synthetic peptide strategy has been used many times to define active
sites and produce active analogs of many proteins, most of which are
considerably more complex than NGF.  Indeed, our initial studies with
NGF peptides suggest that this method will be successful with NGF as
well.

The specific aims during the proposed grant period will be: 1) To
synthesize and purify NGF peptides and analogs derived from peptides
which are active. 2) To test these peptides and analogs for their
ability to mimic or inhibit three well-characterized activities of NGF
in vitro. 3) To test the most potent peptides for their ability to
compete with NGF's binding at its receptor.

## Key facts

- **NIH application ID:** 3121812
- **Project number:** 1R01AG009873-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** FRANK M LONGO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $96,809
- **Award type:** 1
- **Project period:** 1991-05-01 → 1994-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121812

## Citation

> US National Institutes of Health, RePORTER application 3121812, AGING & NEURONAL DEATH--FIRST GENERATION OF NGF ANALOG (1R01AG009873-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121812. Licensed CC0.

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