# Development of promoters of dendritic spine formation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $351,857

## Abstract

Project Summary
 The public health impact of patients suffering from neurodegenerative disorders such as Alzheimer
disease (AD) is increasing at an alarming rate, both in the US and globally. Projections of the economic
burden and lost productivity vary widely, but all estimates are disturbingly high. It is believed, for instance, that
the number of patients diagnosed with AD will rise from the current value of 20-25 million worldwide to up to
three times that number by 2050, assuming no effective treatment strategy emerges. Current approaches to
try to curb the decline of cognitive function in AD, such as anti-amyloid immunotherapy, are showing only
modest effect in the most recent clinical trials. Therefore, there is an immediate need to explore novel
approaches to intervene or reverse the neuropathic effects associated with AD and related diseases.
 Among the most overt clinical symptoms of patients suffering from AD is the significant loss of memory
and the inability to recall newly learned information. We hypothesize that a method that can improve memory
and learning may, therefore, be an effective strategy to reverse the effects or slow down the progression of
neurodegenerative diseases such as AD. In an effort to explore such a novel strategy, we have recently
developed a synthetic molecule with drug-like properties (BTA-EG4) that exhibits the capability of improving
memory and learning in wild type mice and in an AD mouse model and was also found to promote dendritic
spine formation in neurons (in vivo and in vitro). Since dendritic spine density correlates strongly with memory
and learning in human development, we hypothesize that the improved memory and learning in mice treated
with BTA-EG4 is related to the capability of the molecule to promote spinogenesis. In order to follow up on
these initial findings, this research seeks to gain a broader understanding of the activity of BTA-EG4 and
related compounds. We will seek to better characterize the cellular machinery that is affected by BTA-EG4.
Exciting preliminary data shows that we have tentatively identified the cellular target for BTA-EG4 through
photoaffinity pulldown assays. This proposal seeks to 1) validate the cellular target of BTA-EG4 that leads to
increase in dendritic spine density, 2) develop a family of BTA analogs to better characterize their capability to
promote dendritic spines and to optimize spinogenic activity, and 3) explore whether BTA analogs can promote
dendritic spine density in human neurons.
 The overall goal of this research will be the elucidation of the molecular mechanism of action of the
BTA compounds that leads to an increase in dendritic spine density. A direct outcome of this research will be
the identification of a new avenue for drug development leading to improved cognitive performance, which
would represent an important and currently unavailable resource for the management of human mental health.

## Key facts

- **NIH application ID:** 9961453
- **Project number:** 5R01AG053577-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jerry Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $351,857
- **Award type:** 5
- **Project period:** 2016-08-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961453

## Citation

> US National Institutes of Health, RePORTER application 9961453, Development of promoters of dendritic spine formation (5R01AG053577-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9961453. Licensed CC0.

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