# Synaptic function of BK channel-interacting proteins

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2023 · $391,700

## Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder inflicting many people. Most cases of early-onset
familial AD are linked to mutations of presenilins. Previous studies on presenilins have focused on their roles in
the generation of amyloid β (Aβ) because accumulation of Aβ plaques in brain tissue is generally considered the
primary cause of AD. However, the amyloid hypothesis is being questioned because all anti-amyloid clinical trials
have failed. Therefore, it is necessary to explore other potential mechanisms of presenilin function in AD. Among
the known effects of presenilin mutations are reduced neurotransmitter release and calcium dyshomeostasis,
which are both putative underlying mechanisms of AD. It is known that mutations of presenilins cause reduced
neurotransmitter release and calcium dyshomeostasis, which are associated with and potentially caused by
decreased ryanodine receptor expression. However, it is unknown how presenilins regulate ryanodine receptors.
This proposal is to test the hypothesis that presenilins regulate ryanodine receptor expression by acting through
some other regulatory proteins. The nematode Caenorhabditis elegans is used as an animal model to identify
the putative regulatory proteins because many cellular mechanisms in mammalian systems, including the roles
of presenilins in synaptic and ryanodine receptor function, are conserved in worms. The specific aims of this
proposal are: 1) identify candidates for the putative regulatory proteins of ryanodine receptor expression by mass
spectrometry and RNA-seq, and 2) determine whether the identified proteins are required for presenilins’ roles
in neurotransmitter release and ryanodine receptor expression. Our long-term goal is to illustrate whether and
how reduced neurotransmitter release and ryanodine receptor function play a role in the pathogenesis of AD
caused by presenilin mutations.

## Key facts

- **NIH application ID:** 10712011
- **Project number:** 3R01MH085927-12S1
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** ZHAO-WEN WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $391,700
- **Award type:** 3
- **Project period:** 2009-12-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10712011

## Citation

> US National Institutes of Health, RePORTER application 10712011, Synaptic function of BK channel-interacting proteins (3R01MH085927-12S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10712011. Licensed CC0.

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