# Studies of SLC41A1, a Mg2+-Transporting Protein Linked to Parkinson's Disease

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2024 · $371,180

## Abstract

Project Summary/Abstract
 Magnesium has been largely overlooked in neurobiology as a “housekeeping” ion, but this view is directly
challenged by evidence which shows that mutations in Mg2+ transporting proteins are associated with
neurodegeneration. Mutations in the Mg2+ transporting protein SLC41A1 are associated with both increased and
decreased risk of Parkinson's disease (PD). SLC41A1 might therefore be a causative gene for PD. Despite this,
little is known about SLC41A1. For example, we do not yet know if it causes rapid changes in free cytosolic Mg2+
(like an ion channel) or if it works to maintain the levels of free cytosolic Mg2+ within the range required for normal
cellular function (like a transporter). This distinction is required both to define the role of SLC41A1 in the Mg2+
homeostasis and its role in PD pathogenesis. Furthermore, a cellular role for SLC41A1 has not been determined
and it is therefore not known how its dysfunction might lead to PD.
 We hypothesize that SLC41A1 is a Mg2+-permeable ion channel which, through its role in maintaining
the cellular Mg2+ homeostasis, helps maintain the mitochondrial membrane potential and ensures that ATP
production via oxidative phosphorylation proceeds undisturbed. In this application for a Stephen I. Katz ESI
grant, we propose to use liposomal flux assays and lipid bilayer studies as well as electron cryo-microscopy
(cryo-EM) to determine how SLC41A1 mediates Mg2+ transport, and to generate a model to determine its cellular
role.
 Neuronal Mg2+ transport has thus far been virtually untouched by biophysical and structural investigation
and the study proposed here represents the first steps towards understanding the molecular mechanisms of
neuronal Mg2+ homeostasis as well as the Mg2+-dependent molecular origins of neurodegenerative disorders. In
the long term, this study of SLC41A1 has the potential to lead to novel treatments of and preventative strategies
against PD, a debilitating disease which costs the US health system more than $14 billion each year.

## Key facts

- **NIH application ID:** 10894939
- **Project number:** 5R01NS126211-02
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Lejla Zubcevic
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $371,180
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894939

## Citation

> US National Institutes of Health, RePORTER application 10894939, Studies of SLC41A1, a Mg2+-Transporting Protein Linked to Parkinson's Disease (5R01NS126211-02). Retrieved via AI Analytics 2026-08-01 from https://api.ai-analytics.org/grant/nih/10894939. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*