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The Death March of the Prion Protein

CellTweets #5
February 15, 2012 

The mad cow disease, or bovine spongiform encephalopathy (BSE), outbreak that burst into the news in the United Kingdom in the late 1980s is caused by a harmful version of the prion protein. In affected cows, the misfolded prion protein results in the degeneration of the nervous system and eventual death. Alarmingly, the incidence of the human version of BSE, known as Creutzfeld-Jakob Disease (CJD), increased following the bovine epidemic, indicating that the disease could transfer from one species to another. How the misfolded version of the prion protein causes these neurodegenerative diseases is currently not understood. 

The everyday function of the prion protein is the subject of much debate.  The protein is normally found on the surface of cells and may be involved in communication between brain cells. In the 15th December edition of Molecular Biology of the Cell, Vincenzo Mattei and colleagues describe a new role for the normal prion protein in cell death.  

Cells die in a number of ways. One of the most common is a programmed form of cell suicide called apoptosis. This type of cell death is important for the proper development of many tissues and organs, and normal function of the immune function.  When cells undergo apoptosis, they initiate a set of defined reactions that lead to the disruption of the powerhouse of the cell, the mitochondrion, and ultimately cell death.  The authors report that once a cell is triggered to undergo apoptosis, an early event in this process is the movement of the prion protein from the periphery of the cell, along the cytoskeleton to the mitochondria.  At the mitochondria, the prion protein causes disruption and subsequent cell death.  Importantly, reducing the level of the prion protein or preventing its proper localization protects cells from mitochondrial disruption and apoptosis.  So, the normal prion protein plays an important role in regulated cell death, this may help to understand how the harmful form of this protein causes neuronal cell death in disease.  –Gavin McStay

Key Terms:

MBoC Reference:

Larimore, J., Tornieri, K., Ryder, P.V., Gokhale, A., Zlatic, S.A., Craige, B., Lee, J.D., Talbot, K., Pare, J.F., Smith, Y., and Faundez, V. (2011) The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse. Mol Biol Cell, 22(24) 4854-4867.

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