L1CAM: a potential role in Alzheimer pathology

L1-type cell adhesion molecule (L1-CAM) is a synaptic membrane protein that is associated with L1 syndrome, which exhibits spasticity, intellectual disability and hydrocephalus Neuroglian (Nrg) is the invertebrate homologue of L1-CAM in Drosophila melanogaster. In vitro studies have shown L1-CAM is proteolytically cleaved and the intracellular domain (ICD) translocates to the nucleus. There it is involved in the upregulation of genes that are involved in DNA damage response, cell cycle progression, apoptosis and cellular differentiation. In some forms of Alzheimer’s Disease (AD) proteolytic cleavage of L1-CAM are enhanced. We studied the effects of expression of NrgICD in vivo. Our results indicate that ubiquitous expression of NrgICD like its vertebrate homologue resulted in upregulation of NBS1 and c-myc in Drosophila. We found that the ubiquitous expression of NrgICD resulted in reduced viability in various models of oxidative stress. This suggests that enhanced proteolytic cleavage of Nrg/L1-CAM contributes to the pathology of AD. Our results may provide new insights into the cellular mechanisms of neurodegenerative diseases.