Altered expression of atypical PKC and Ryk in the spinal cord of a mouse model of amyotrophic lateral sclerosis

Dev Neurobiol, 2014 · DOI: 10.1002/dneu.22137 · Published: August 1, 2014

Simple Explanation

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of motor neurons. The study focuses on Wnt signaling components, atypical PKC (aPKC) and a Wnt receptor, Ryk, in a mouse model of ALS. aPKC mediates Wnt signaling to regulate axon differentiation and cell survival, while Ryk is a Wnt repulsive receptor that regulates axon guidance and inhibits regeneration after spinal cord injury. The study found altered expression of aPKC and Ryk in the spinal cord of SOD1 (G93A) mice, suggesting that changed Wnt signaling may contribute to neurodegeneration in ALS.

Study Duration

Not specified

Participants

SOD1 (G93A) mice

Evidence Level

Not specified

Key Findings

1
aPKC expression was increased in motor neurons of the lumbar spinal cord in SOD1 (G93A) mice at different stages, and colocalized with SOD1 in motor neuron cell bodies and extracellular aggregates.
2
Biochemical fractionation showed that aPKC protein level was increased in the detergent-insoluble protein fraction in SOD1 (G93A) mice at late stage but decreased in the detergent-soluble fraction at symptomatic stage.
3
Ryk expression was also increased in the motor neurons and the white matter in the ventral lumbar spinal cord of mutant SOD1 mice with a peak at early stage.

Research Summary

This study examined the expression patterns and levels of aPKC and Ryk in the lumbar spinal cord of SOD1 (G93A) mice, a model of ALS. The researchers found that aPKC was upregulated in motor neurons at all stages of disease progression and detected in extracellular SOD1 aggregates, increasing with disease progression. Ryk was also increased in motor neuron cell bodies and axons, suggesting that altered Wnt signaling pathways might contribute to the pathogenesis of ALS.

Practical Implications

Therapeutic Targets

Further studies could identify new therapeutic targets by understanding the mechanisms mediating axon guidance and plasticity.

Disease Mechanisms

Understanding how disruption of aPKC and Ryk functions contributes to ALS will shed light on the disease mechanisms.

Wnt Signaling Role

More studies on the role of Wnt signaling in ALS could provide insights into the etiology and pathogenesis of the disease.

Study Limitations

1
The significance of increased aPKC immunoreactivity is currently unknown.
2
Whether aPKC has a pro-apoptotic function in neurons, similar to its function in ovarian cancer, needs further investigation.
3
The specific mechanisms by which altered Wnt signaling contributes to ALS pathogenesis require further elucidation.

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