The huntingtin protein in Huntington disease

Author(s):
Schut, M.H.
Published
2017
Publication type
Doctoral Thesis

Abstract

Huntingtin disease (HD) is

an autosomal dominant inheritable disease that mainly affects the brain. HD is

caused by expansion of a CAG repeat within exon 1 of the huntingtin gene giving

rise to the expression of a mutant huntingtin protein with an elongated polyQ repeat at it's N-terminus. Mutant huntingtin is prone to aggregation and is believed to invoke toxicity, especially by the formation of N-terminal fragments. The first part of this thesis describes the selection and characterization of Llama VHH antibody fragments against N-terminal huntingtin. The second part of this thesis consists of studies on huntingtin in human (brain) tissue regarding N-terminal fragments, huntingtin aggregation and mutant versus wild-type huntingtin expression levels.

Huntington HDZvH HRMA VHH N-terminalAggregation ExpressionRNA Protein
Defense date
2017-09-20
Language
English
Supervisor(s)
Ommen, G.J.B. van
Advisor(s)
Roon-Mom, W.M.C. van
Committee member(s)
Aartsma-Rus, A.M.; Roos, R.A.C.; Temel, Y.; Reits, E.A.J.
Qualification
Ph.D.
Degree granting institution
Humane Genetica, Medicine / Leiden University Medical Center (LUMC), Leiden University, Leiden
hdl
1887/57979
ISBN(s)
9789402807035

Funding

Sponsorship
Prinses Beatrix Fonds, Bontiusstichting