The Proteolipid Protein and its Possible Role in the Pathology of Multiple Sclerosis
Latham, Amy E.
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Multiple sclerosis is a neurological disorder wherein myelin in the central nervous system (CNS) is destroyed through a chronic inflammatory process. The cause of the inflammation is not known, but is believed to be a result of an autoimmune process in which autoreactive T lymphocytes attack the myelin. Oligodendroglia, the cells which supply myelin in the CNS, are largely comprised of the proteolipid protein (PLP). Relatively little is known about PLP because it is difficult to work with due to its high hydrophobicity, but new techniques using fusion constructs have elucidated its importance to cells. In this experiment, a series of mammalian expression vectors that used either the CMV (constitutive mammalian) promoter or a bacterial tetracycline regulated promoter called the PLP Tet-On promoter were created to examine the processing of normal and mutant PLP proteins. Results indicate that in the 293 human embryonic kidney cell, PLP is regulated beyond the translational level by the ubiquitinlproteasome system. Current theory claims that the peptides resulting from PLP proteasome degradation are recognized as antigenic by the immune system and that oligodendrocytes displaying these peptides are targeted for cell death by autoreactive T lymphocytes. This knowledge provides important information about the activities ofPLP in the cell and may help demonstrate that PLP is the principle protein involved in the oligodendrocyte death that leads to the pathology of multiple sclerosis.