"These observations provide the first visual study of this cell survival activity," said Morimoto, whose team studied the chaperone Hsp70 (a heat shock protein) and polyglutamine aggregates, the type of protein aggregate responsible for Huntington's disease. "The molecular chaperones are not like other proteins."
In order to visualize the behavior of chaperones and aggregates in an animal, the researchers use human tissue culture cells and C. elegans, a transparent roundworm whose biochemical environment is similar to that of human beings and whose genome, or complete genetic sequence, is known.
Although the Northwestern researchers are studying Huntington's disease, these experimental models can be used to study other neurodegenerative diseases because of the common molecular components.
Proteins, made up of different combinations of amino acids, are basic components of all living cells. To do its job properly, each protein first must fold itself into the proper shape. In this delicate process, the protein receives its folding instructions from its amino acid sequence and is assisted by a class of proteins known as heat shock proteins or molecular chaperones that function to prevent misfolding, or, in the case of already misfolded proteins, to detect them and prevent their further accumulation.
In Huntington's disease, for example, a mutated gene directs production of a protein with an increasing number of consecutive residues of the amino acid glutamine. When the number of residues expands past 40, the protein exhibits unusual biochemical properties, causing the protein to misfold. This results in a loss of function and protein aggregation -- in other words, disease.
Contact: Megan Fellman