It is identified that Cdc42 activation in disease-state neurons may be deleterious and 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.
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.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by progressive loss of motor neurons (MNs).
N
6
-methyladenosine (m
6
A) is the most abundant mRNA modification, yet its role in ALS MNs degeneration remains poorly understood. In this study we observed a significant...
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MAPT (Tau) dysregulation is implicated in several neurodegenerative diseases, but its contribution to amyotrophic lateral sclerosis (ALS) is poorly understood. Here we show that mRNA isoforms encoding 4-repeat (4R) Tau are upregulated and cytoplasmically enriched in iPSC-derived motor neurons (MNs) from VCP-mutant and...
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OBJECTIVE
Early phenotypic presentation of central afferent synapse dysfunction within patients with spinal muscular atrophy (SMA) represents a key target for therapeutic development; however, the underlying disease mechanisms remain unresolved. By further investigating motor neuron synapse and peri-synaptic astrocyte...
Emily Welby, Xiao-Jie Liu, Melinda Wojtkiewicz et al.· Annals of Neurology· 0 citations
Annexin A1 (ANXA1) is a multifunctional regulatory protein involved in neuroinflammation and cellular homeostasis, but its role in amyotrophic lateral sclerosis (ALS) remains unclear. In this study, we investigated the relationship between ANXA1 and Hippo pathway signaling in ALS. Bioinformatic analysis of transcriptom...
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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by motor neuron loss and has been genetically linked to mutations in RNA-binding proteins. A mutation D262V in the RNA-binding protein hnRNPA1, found in a subset of ALS patients, causes widespread splicing pattern changes. Cells expr...
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