Date of Award

Spring 6-12-2026

Document Type

Masters Thesis

Degree Name

M.S. in Biological Sciences

Organizational Unit

College of Natural Science and Mathematics, Biological Sciences

First Advisor

Daniel A. Linseman

Second Advisor

Daniel A. Paredes

Third Advisor

Xi Yang

Fourth Advisor

Scott Horowitz

Copyright Statement / License for Reuse

All Rights Reserved
All Rights Reserved.

Keywords

Amyotrophic lateral sclerosis (ALS), Cdc42 inhibition, G93A-SOD1, Motor neuron, Muscle paralysis, Neurodegeneration

Abstract

Amyotrophic lateral sclerosis (ALS) is a highly progressive neurodegenerative disease affecting motor neurons (MNs) in the motor cortex, brain stem, and spinal cord. Patients ultimately succumb to muscle paralysis by mechanisms of MN axonal retraction, denervation from neuro-muscular junctions (NMJs), and neuronal apoptosis. Previous research has demonstrated that Rho family GTPases, Rac and Rho, are involved in mechanisms of neurite extension, retraction and cell survival, however it remains to be investigated whether Rho GTPase actin-cytoskeleton modulator, Cdc42, plays a role in ALS disease progression. In studying G93A-SOD1 NSC-34 motor neuronal cells treated with Cdc42 inhibitor, ZCL367, we identified that Cdc42 activation in disease-state neurons may be deleterious. Additionally, Cdc42 inhibitors, ZCL367 and high-dose ZCL279, appear to be neuroprotective against the selective degeneration of α-MNs in the ventral horn of G93A-hSOD1 transgenic (Tg) mice.

Copyright Date

6-2026

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Rights Holder

Valorie D. Myhre

Provenance

Received from ProQuest

File Format

application/pdf

Language

English (eng)

Extent

57 pgs

File Size

906 KB

Download

Available for download on Tuesday, July 20, 2027



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