Effects of FYN3 and PP2, Inhibitors of FYN, on Proliferation and Morphology of Neuroblastoma Cells
Hodkinson, Rebecca L.
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Alzheimer's Disease is the fourth leading cause of death in developed countries, yet its molecular causes are still unclear. The brains of patients with this devastating disease exhibit cells bunched up in knots, called neurofibrillary tangles, and cellular debris that surrounds neurons, called senile plaques. Considerable research has focused on the properties of the amyloid-beta protein, which make the senile plaques. Amyloidbeta (A𝛽-40) is a naturally occurring, nontoxic peptide. However, raised levels of a slightly larger version of this peptide, A𝛽-42, are found in the brains of patients with Alzheimer's disease. Recently, Lambert et al. (1998) discovered that A𝛽-42 aggregates were toxic to nerve cells grown in vitro and resulted in cell death. However, in the absence of cellular tyrosine kinase Fyn, A𝛽-42 aggregates were less toxic. This finding suggested that the amyloid-beta protein isoform and Fyn may be involved in normal neuronal physiology. However, little is known about the exact role of Fyn in neuron function. This study tested the responses of neurons when Fyn was blocked under normal conditions. We proposed that Fyn inhibition would retard cell proliferation. Fyn inhibition was accomplished using two Fyn inhibitors, PP2 and FYN3. Based on cell growth and morphology observations, we discovered that inhibition of Fyn slowed and, sometimes, decreased proliferation. The results suggested that Fyn was necessary for neuronal growth. More detailed studies will be necessary to establish how Fyn performs, which may provide insight on the understanding of Alzheimer's disease.