Neurodegenerative disease: mechanism that causes cell death

Posted by: joann on May 31, 2006 - 01:02 PM
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[excerpt] Misfolded and damaged proteins are common to all human neurodegenerative diseases. Clumps of these aggregated proteins destroy neurons within the brain and cause disease. But explanations for the mechanism that actually causes cell death have varied widely, puzzling scientists and leading them to ask whether Alzheimer's, Parkinson's, Huntington's and Creutzfeldt-Jakob diseases and familial amyotrophic lateral sclerosis are related diseases or very different diseases.

Researchers at Northwestern University have offered a clue that may get to the core of the cell death question and establish a common mechanism in these diseases.

In a study, published in the journal Science, the research team showed that polyglutamine ( the toxic component of the protein responsible for Huntington's disease ) is so demanding on the cell's system that it changes the environment within the cell, causing other metastable, or partially folded, proteins to crash and lose function. Over time, this can cause the organism to die.

" Our results suggest that these disease-associated, aggregation-prone proteins may exert their destabilizing effects by interfering generally with other proteins that are having difficulty folding," said Richard I. Morimoto, who led the study.

" We found that the system for protein quality control is not robust at all -- it is very delicate," said Morimoto. " Slight changes in the cell's environment have huge consequences. A single mutant polyglutamine protein interferes with the folding and functioning of very different types of proteins in the cell. This, in turn, could interfere with innumerable cellular processes and offers an explanation of why so many different mechanisms have been proposed for toxicity and cell death."

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