# Sushi domain proteins as synapse protective factors in brain development and aging

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2022 · $330,068

## Abstract

Project Summary/Abstract
 Synapse formation and elimination are fundamental processes that is essential for the assembly of neural
circuits in the brain during development. Defects in these processes result in abnormal synaptic densities in the
brain, which is believed to contribute towards the pathogenesis of many neurodevelopmental disorders. The goal
of the proposed research is to understand how Sushi Repeat Protein X-linked 2 (SRPX2) regulates synapse
density in the brain. We have previously shown that the sushi repeat protein X-linked 2 (SRPX2) gene codes for
a neuronally-expressed secreted synaptogenic protein that increases the density of excitatory synapses in cor-
tical neurons. Sushi repeats are predominantly found in known complement regulators in the periphery. Our
preliminary data suggests that SRPX2 inhibits complement activation in the brain, thereby decreasing synapse
pruning and increasing synapse density. To test this hypothesis, we proposed the following aims. Aim 1: Deter-
mine if SRPX2 signals through the classical complement pathway to regulate synapse density and elimination.
Aim 2: Determine if SRPX2 inhibits the classical complement cascade by binding to C1q. Aim 3: Determine if
SRPX2 is required in the adult and aged brain for synapse maintenance. We anticipate that these studies will
provide new insights into the molecular mechanisms underlying synapse elimination in the developing brain, and
may lead to novel therapeutic approaches for treating developmental and degenerative brain disorders.

## Key facts

- **NIH application ID:** 10330454
- **Project number:** 5R01NS112389-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Gek Ming Sia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $330,068
- **Award type:** 5
- **Project period:** 2019-05-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330454

## Citation

> US National Institutes of Health, RePORTER application 10330454, Sushi domain proteins as synapse protective factors in brain development and aging (5R01NS112389-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10330454. Licensed CC0.

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