Improper Protein Shape May Lead to Brain Cell Death
Posted February 1, 1998
Proteins consist of one or more long chains of amino acids. These chains coil or bend into a specific shape that is related to the function of the protein. If the
shape of the protein is changed, the function of the protein is usually altered. The shapes of the proteins are ultimately determined by the types of amino acids that make up the chains.
Researchers have found that some diseases of the brain, including Huntington's disease (an inherited nervous system disorder) and spinocerebellar ataxia (a disorder
that results in loss of body balance) are due to abnormal proteins. In all of the diseases studied so far, there is an improper aggregation of proteins in the nucleus of the neurons
of the brain. This clumping results in a disruption of the function of the brain cell nucleus. Eventually these brain cells die.
The proteins in the brain cells of people afflicted with these diseases have been found to contain an abnormal number of repeated glutamines. Glutamine is one of
the 20 amino acids that can be used as building blocks of proteins. These 30 to 40 repeated glutamines are responsible for the clumping of the proteins that form aggregates in the nucleus
of brain cells. These inclusions presumably are linked to cell death. Scientists hypothesize that the nucleus may not be able to break these proteins down. The abnormal proteins also
recruit other normal proteins into their aggregates.
Researchers do not know what the link is between the abnormal proteins and the eventual death of neurons in the brain. If there is a link, scientists hope to
find a possible therapy that could block the movement of these proteins into the nucleus or block the aggregation of these proteins. It is still a mystery why the aggregations kill the
cell, but blocking them may prevent the death of brain neurons and ease or delay the symptoms of Huntington's and other diseases.
Das, S. S., H. L. Paulson, M. K. Perez, Y. Trottier, J. Q. Trojanowski, S. H. Subramony, P. Vig, J. L. Mandel, K. H. Fischbeck, and R. N. Pittman. "Intranuclear
Inclusions of Expanded Polyglutamine Protein in Spinocerebellar Ataxia Type 3." Neuron, Vol. 19, August 1997, pp. 333-344.
Bates, Gillian P., Eberhard Scherzinger, Rudi Lurz, Mark Turmaine, Laura Mangiarine, Birgit Hollenbach, Renate Hasenbank, Stephen W. Davies, Has Lehrach, and Erich
E. Wanker. "Huntington-Encoded Polyglutamine Expansions Form Amyloid-like Protein Aggregates In Vitro and In Vivo." Cell, Vol. 90, 1997, pp. 549-558.