Huntington’s disease is a genetically based, severe neurodegenerative disorder that results in progressive motor, cognitive and psychiatric impairment and, ultimately, death. It is caused by an expanded CAG triplet repeat producing a mutant huntingtin protein with a polyglutamine-repeat expansion. There is no effective treatment for Huntington’s, which, like many neurodegenerative diseases, is characterized by an accumulation of misfolded mutant proteins that interfere with brain function.
Here, Tan and colleagues report that synthetic polyglutamine oligomers and cerebrospinal fluid from BACHD transgenic rats and from human Huntington’s disease subjects can seed mutant huntingtin aggregation in a cell model and its cell lysate. This assay distinguishes symptomatic Huntington’s disease subjects – who have high seeding activity – from gene carriers not yet showing symptoms – who have lower seeding activity. Fluid samples from non-Huntington disease individuals do not exhibit this seeding property.
By identifying in spinal fluid how the characteristic mutant proteins of Huntington’s disease spread from cell to cell, Tan and colleagues have created a new method to quickly and accurately track the presence and proliferation of these neuron-damaging compounds – a discovery that may accelerate the development of new drugs to treat this incurable disease.
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Tan Z, Dai W, van Erp TG, Overman J, Demuro A, Digman MA, Hatami A, Albay R, Sontag EM, Potkin KT, Ling S, Macciardi F, Bunney WE, Long JD, Paulsen JS, Ringman JM, Parker I, Glabe C, Thompson LM, Chiu W and Potkin SG: Huntington’s disease cerebrospinal fluid seeds aggregation of mutant huntingtin. Molecular Psychiatry [Epub ahead of print, June 23, 2015; doi: 10.1038/mp.2015.81.].
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http://www.ncbi.nlm.nih.gov/pubmed/26100538