Soluble N-terminal fragment of mutant Huntingtin protein impairs mitochondrial axonal transport in cultured hippocampal neurons

Neuroscience Bulletin
Jun TianBao-Rong Zhang

Abstract

Huntington's disease (HD) is an autosomal dominant, progressive, neurodegenerative disorder caused by an unstable expansion of CAG repeats (>35 repeats) within exon 1 of the interesting transcript 15 (IT15) gene. This gene encodes a protein called Huntingtin (Htt), and mutation of the gene results in a polyglutamine (polyQ) near the N-terminus of Htt. The N-terminal fragments of mutant Htt (mHtt), which tend to aggregate, are sufficient to cause HD. Whether these aggregates are causal or protective for HD remains hotly debated. Dysfunctional mitochondrial axonal transport is associated with HD. It remains unknown whether the soluble or aggregated form of mHtt is the primary cause of the impaired mitochondrial axonal transport in HD pathology. Here, we investigated the impact of soluble and aggregated N-terminal fragments of mHtt on mitochondrial axonal transport in cultured hippocampal neurons. We found that the N-terminal fragment of mHtt formed aggregates in almost half of the transfected neurons. Overexpression of the N-terminal fragment of mHtt decreased the velocity of mitochondrial axonal transport and mitochondrial mobility in neurons regardless of whether aggregates were formed. However, the impairment of mitochondrial ...Continue Reading

References

May 1, 1993·Journal of Neurology, Neurosurgery, and Psychiatry·E SpargoP L Lantos
Sep 2, 2004·Molecular and Cellular Biology·Eugenia TrushinaCynthia T McMurray
Feb 14, 2006·Neurobiology of Disease·Diane T W ChangIan J Reynolds
Mar 14, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Adam L OrrXiao-Jiang Li
Jul 29, 2010·Physiological Reviews·Chiara ZuccatoElena Cattaneo
Nov 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lynsey G BilslandGiampietro Schiavo
Dec 21, 2011·The Journal of Biological Chemistry·Joseph CichonGong Chen
Dec 28, 2011·Experimental Neurology·Montserrat Arrasate, Steven Finkbeiner
Jan 6, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Elaine Waldron-RobyChristopher A Ross
Apr 10, 2012·Progress in Neurobiology·Lawrence S B Goldstein
May 24, 2012·Journal of Cell Science·William M Saxton, Peter J Hollenbeck
Jul 13, 2012·Cleveland Clinic Journal of Medicine·Carlos Singer
Jul 10, 2012·Current Opinion in Neurology·Ainhi D Ha, Victor S C Fung
Nov 20, 2012·Trends in Cell Biology·Kie ItohHiromi Sesaki

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Citations

Aug 1, 2015·Movement Disorders : Official Journal of the Movement Disorder Society·Kathleen M Shannon, Avram Fraint
Jul 24, 2021·Frontiers in Molecular Biosciences·Thomas PaßDavid Pla-Martín

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