# SUMOylation of Voltage-Gated Sodium Channels In Neuronal Hyperexcitability of Alzheimer’s Dementia

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2022 · $386,250

## Abstract

Modification of neuronal ion channels by Small Ubiquitin-like Modifiers (SUMOs) has been
observed in brains of patients with Alzheimer’s Dementia (AD). However, the functional
consequences of SUMOylation of neuronal ions channels, and the role of SUMOylation in
alterations in neuronal electrophysiology observed in AD, remain largely unknown.
Neuronal hyperexcitability contributes to the cognitive defects in AD. Neuronal voltage-gated
sodium channels (Nav1.1/1.2/1.6) are integral to neuronal excitation. Moreover, β-amyloid (Aβ)
peptides, which play a causal role in AD, alter the physiological properties and/or expression of
neuronal voltage-gated sodium channels. Our prior work, which forms the basis of the parent
grant, has shown that SUMOylation of the cardiac voltage-gated sodium channel Nav1.5 alters
channel properties, leading to an increase in the inward sodium current. The functionally relevant
SUMOylation motif we have identified in Nav1.5 is highly conserved among voltage-gated sodium
channels, including neuronal voltage-gated sodium channels. This suggests that physiology of
neuronal voltage-gated sodium channels is also subject to modification via SUMOylation.
In this supplement we will investigate the role of SUMOylation in regulating the functional
properties of neuronal voltage-gated sodium channels using state-of-the-art electrophysiological
methodologies, as well as novel SUMO-modifying reagents generated in the parent grant.
Therefore, this application falls within the scope of the parent grant. This supplement will also
explore whether SUMOylation can modulate neuronal excitability in the context of β-amyloid
toxicity through its impact on the post-translational landscape, surface expression, and
conductance properties of neuronal voltage-gated sodium channels.
These studies will open a new chapter in understanding how deregulation of neuronal excitability
via SUMOylation of neuronal sodium channels contributes to the pathogenesis of cognitive
impairment in AD.

## Key facts

- **NIH application ID:** 10496581
- **Project number:** 3R01HL115955-07S1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Kaikobad J. Irani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $386,250
- **Award type:** 3
- **Project period:** 2013-06-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10496581

## Citation

> US National Institutes of Health, RePORTER application 10496581, SUMOylation of Voltage-Gated Sodium Channels In Neuronal Hyperexcitability of Alzheimer’s Dementia (3R01HL115955-07S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10496581. Licensed CC0.

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