The behaviour of long polyglutamine-containing proteins in mammalian PC12 cells

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The behaviour of long polyglutamine-containing proteins in mammalian PC12 cells

Project report in partial fulfilment for the degree of MSc in Neuroscience August 2008

Janahi Visakan

Supervised by Dr Angela Hodges

Department Of Neuroscience

Institute of Psychiatry

King's College London

University Of London

The behaviour of long polyglutamine-containing proteins in mammalian PC12 cells

Abstract

Huntington's disease is an autosomal dominant, inherited neurodegenerative disorder induced by a glutamine expansion repeat at the N-terminal end of the huintingtin protein. These N-terminal fragments of huntingtin aggregate in the nucleus and destroy cells. This genetic disorder is accompanied by motor, cognitive, personality changes and psychiatric symptoms. If the number of glutamine residues increase to more than 37, then this induces an adult, onset gradual progressive neurodegeneration known as HD.The genome of D.discoideum, a social amoeba consists of polyglutamine fragments longer than 40 residues. These long polyglutamine fragments do not confer any toxic effects .In addition the genome sequencing of D.discoideum has demonstrated that this organism is able to withstand a large number of proteins containing long polyglutamine stretches. A synthetically generated CAAX repeat construct was clone d into a mammalian expression vector using