# The Role of Copper in Choroid Plexus

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $502,292

## Abstract

PROJECT SUMMARY
Copper (Cu) has a critical and multifaceted role in the development and function of mammalian brain. Cu
misbalance is observed in many disorders affecting the central nervous system: Menkes disease, Wilson
disease, Alzheimer’s and Parkinson’s diseases, multiple sclerosis, and others. With the exception of Menkes
disease, for most of these disorders the origin of Cu misbalance in the brain is not well understood, and
whether Cu fluxes in and out of the brain are compromised remains unknown. The information about Cu entry
into the healthy brain is also very limited. The proposed program of studies will clarify the mechanism
regulating Cu transfer through choroid plexus (ChPl), an important secretory tissue, which produces
cerebrospinal fluid and forms the brain-cerebrospinal fluid barrier. Studies under Specific Aim 1 will determine
the role of ChPl in Cu entry into the perinatal brain. The abundance, localization, and functional interactions
between the Cu transporters Atp7a, Atp7b, and Slc31a1(Ctr1) as well as endogenous Cu chelators,
metallothioneins, will be characterized at different time points of healthy brain maturation, and these
characteristics will be compared for control and Atp7b-/- mice, an animal model of Wilson disease. Targeted
deletion of Ctr1 and Atp7a in mouse ChPl epithelium will be used to measure contribution of ChPl to Cu
transport into the perinatal brain. Specific Aim 2 will identify the mechanistic link between Cu homeostasis in
ChPl, organization of ChPl cytoskeleton and the development of cilia; this will be achieved using transmission
electron microscopy, immunocytochemistry, and proteomics. The impact of Cu misbalance in Atp7b-/- choroid
plexus on expression and activity of peptidyl-a-amidating mono-oxygenase (PAM), a Cu-dependent enzyme
associated with cilia development will be examined. How changes in Cu homeostasis in ChPl modify the ChPl
secretome will be determined by employing iSLET methodology (in situ Secretory protein Labeling via ER-
anchored TurboID) and mass-spectrometry.

## Key facts

- **NIH application ID:** 10980630
- **Project number:** 1R01NS134958-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** SVETLANA LUTSENKO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $502,292
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980630

## Citation

> US National Institutes of Health, RePORTER application 10980630, The Role of Copper in Choroid Plexus (1R01NS134958-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10980630. Licensed CC0.

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