# Myelin Junction Therapy in Peripheral Neuropathies

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2021 · $367,728

## Abstract

Schwann cell extends its cell membrane to wrap around segments of axon concentrically for multiple layers
and forms the myelin. Demyelination removes segments of myelin along the nerve fibers. This pathology occurs
in a group of neurological disorders with collectively high prevalence: Guillain-Barre syndrome, chronic
inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, hereditary neuropathy with liability
to pressure palsies (HNPP) and multiple sclerosis. Myelin may be abnormally developed (dysmyelination) in
inherited neurological diseases. Therefore, it is highly desirable if molecular targets can be identified and
manipulated to repair myelin. Motivated by our recent observations, we propose this study to deals with myelin
junction proteins and p21 activated kinase (PAK)-related pathway that likely become the molecular target.
 Our studies have discovered that hyperactive p21-activated kinase-1 (PAK1) plays a key role in removal of
myelin junctions in matured myelin. These junctions are made by proteins that seal the small spaces between
layers of myelin. Removal of myelin junctions lead to excessively permeable myelin in a mouse with a deletion
of one of two copies of Pmp22 genes (Pmp22+/-), an authentic model for HNPP. The junction removal is an
early event upstream to the segmental demyelination. In contrast, we recently observed that deficiency of
PAK2 (another family member of PAK in the peripheral nerves) in Schwann cells results in severe
dysmyelination with pathological changes similar to that seen in patients with congenital hypomyelination,
suggesting a critical function of PAK2 in myelin development. Thus, relative levels of PAK1/PAK2 activation
may differentially affect myelin development and maintenance.
 In this study, we will first verify the causal relationship between hyperactive PAK1 and removal of myelin
junctions / demyelination in several peripheral neuropathy mouse models. We will then examine how PAK2
regulates myelin development. Finally, we will test whether PAK can be targeted to treat other peripheral nerve
diseases.
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## Key facts

- **NIH application ID:** 10123024
- **Project number:** 5R01NS115748-02
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** JUN LI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $367,728
- **Award type:** 5
- **Project period:** 2020-03-15 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123024

## Citation

> US National Institutes of Health, RePORTER application 10123024, Myelin Junction Therapy in Peripheral Neuropathies (5R01NS115748-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10123024. Licensed CC0.

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