Mutant HTT aggregation and conformers: what we know and what we don’t know

Add to your list(s) Download to your calendar using vCal

• Erich E. Wanker, Head Neuroproteomics and Molecular Mechanisms of Neurodegenerative Diseases, Max Delbrueck Center for Molecular Medicine (MDC) Berlin-Buch
• Wednesday 21 June 2017, 10:30-11:30
• Department of Chemistry, Cambridge, Unilever lecture theatre.

If you have a question about this talk, please contact Priyanka Joshi.

Self-propagation of amyloidogenic protein aggregates may drive the progression of neurodegenerative diseases including Huntington’s disease (HD). We recently developed of a cell-free, FRET -based mutant huntingtin (mHTT) aggregate seeding (FRASE) biosensor assay that enables the detection and quantification of mHTT seeding activity (HSA) in complex biosamples from HD patients and disease models. Application of FRASE assays revealed HSA in crude brain homogenates of presymptomatic HD transgenic mice and its progressive increase with development of the phenotype, indicating that HSA quantitatively tracks disease progression. Biochemical investigations of mouse brain homogenates demonstrated that HSA is predominantly detectable in soluble protein fractions, which contain small, fibrillar mHTT oligomers. Finally, we assessed the disease relevance of mHTT exon-1 (mHTTex1) seeds in an inducible Drosophila fly model. We demonstrated that the short-time production of seeding-competent mHTTex1 aggregates in fly brains leads to a dramatically reduced lifespan, suggesting that mutant HTTex1 seeds are highly toxic structures. Together, our results suggest a central role of self-propagating mHTT seeds in the development and progression of HD.

This talk is part of the Biophysical Seminars series.

This talk is included in these lists:

• All Talks (aka the CURE list)
• Biophysical Seminar Series 2016/17
• Biophysical Seminars
• Department of Chemistry
• Department of Chemistry, Cambridge, Unilever lecture theatre
• Featured lists
• School of Physical Sciences

Note that ex-directory lists are not shown.