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Large Amounts Of Glutamine As The Cause Of Disease

2067 words - 8 pages

Neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease are caused by the aggregation of abnormal proteins in neurons. An essential component of cellular function is the correct assimilation of proteins in the cell. Proteins fold into specific structures and then carry out cellular functions. However, when this folding process runs amuck, abnormal proteins are introduced into the cell. In neurodegenerative diseases, these protein aggregates are characterized by having genes which contain too many CAG trinucleotides repeats that encode for polyglutamine (polyQ). Having too much polyQ leads to the gene products being converted to a proteotoxic state. All in all, disruptions in protein folding lead to an overabundance of CAG repeats which results in an overproduction of polyQ which raises the toxicity of the cell to levels that effect the cell's functions.

Through experimentation, this paper attempted to find the threshold for the number of CAG repeats that determines whether cellular function will be disrupted by the protein aggregates. Molecular genetic studies have already established than normal chromosomes (and genes) contain fewer than 30-34 CAG repeats. This paper attempted to prove that 35-40 CAG repeats results in cellular toxicity levels that severely disrupt cellular function.

To address the connection between the CAG threshold (thus, the polyQ aggregation) and cellular toxicity, a species of worm, Caenorhabditis elegans, was used during experimentation. (C. elegans are good model organisms to study human neurodegenerative disease not only because C. elegans' neurons resemble vertebrate neurons at cellular and molecular levels, but also because many genes are conserved between worms and humans.) By testing different CAG repeat lengths, the resulting conversion of polyQ aggregates to toxic forms was observed and analized in great detail. Thus the threshold of polyglutamine protein aggregation in cellular toxicity was determined.

Caenorhabditis elegans (abbreviated C. elegans) are nematodes - a member of the phylum Nematoda which includes roundworms and threadworms, and are a phylum of smooth-skinned, unsegmented worms with a long cylindrical body shape tapered at the ends. It includes free-living and parasitic species that are both aquatic and terrestrial. They are small, growing to about 1 mm in length, and live in the soil - especially rotting vegetation - in many parts of the world, where they survive by feeding on microbes such as bacteria. They are of no economic importance to man, but they shares many of the essential biological characteristics that are central problems of human biology.

Plasmids, circular pieces of DNA, were cloned using the method, Polymerase Chain Reaction (PCR). These round DNA were then encoded with extra amino acid, in particular glutamine (or Q) and mixed with the DNA of worms called C. elegans. The worms were also made to be fluorescent so that researchers could see...

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