Investigating the Effects of Atlastin-1 on Spastin and REEP1 Using Primary Cultured Neurons from Mice with Motor Neuron Disease
Edsall, Taryn N.
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Impairment of axonal transport is a common cause of motor neuron degeneration and is associated with many neurological disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), and hereditary spastic paraplegia (HSP). HSP affects approximately 1.27-9.6 per 100,000 people, and pathologically leads to length-dependent retrograde degeneration of corticospinal neurons. Over .half of all cases of autosomal dominant HSP are caused by mutations in spastin, atlastin-1, or REEP1. These proteins co-localize and bind together in the endoplasmic reticulum (ER) via intramembrane hydrophobic hairpin domains and are directly involved in the coordination of ER shaping and microtubule dynamics in corticospinal neurons. To understand the possible effects of eliminating the protein atlastin-1 in mouse models, this study used primary cortical neuron cultures from adult knockout atlastin mice. Immunocytochemistry was performed on these cultured neurons, staining for spastin, atlastin-1, and REEP 1 to determine how the quantity of atlastin affects the location and quantity of spastin and REEP 1, as well as axon length in neurons. While it was confirmed that atlastin levels were significantly less in heterozygous cultures, overall protein levels of spastin and REEP 1 decreased in heterozygous cultures, however they were not statistically significant. Future experimentation with atlastin knockout mice will.allow for an increased understanding of the relationships between axonal transport and motor neuron degeneration, which is imperative for the development of molecular-targeted therapies and biomarkers in HSP, as well as other motor neuron diseases.
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