Neuroscience Graduate Student's Research on Huntington's Disease Featured in Neuron
Jonathan Grima, a Neuroscience Graduate Student in Dr. Jeffrey Rothstein's lab, recently reported his research in Neuron regarding a potential cellular cause for neurodegenerative diseases like Huntington's Disease. Jonathan, and his work, were also featured in a recent Baltimore Sun article.
Baltimore Sun Article: http://www.baltimoresun.com/health/bs-hs-huntingtons-disease-20170404-story.html
Video from Baltimore Sun: http://www.baltimoresun.com/health/92991267-132.html
Article in Neuron:
Mutant Huntingtin Disrupts the Nuclear Pore Complex.
Grima JC et al. Neuron. 2017 Apr 5;94(1):93-107.e6. doi: 10.1016/j.neuron.2017.03.023.
http://www.cell.com/neuron/abstract/S0896-6273(17)30206-4
Abstract
Huntington's disease (HD) is caused by an expanded CAG repeat in the Huntingtin (HTT) gene. The mechanism(s) by which mutant HTT (mHTT) causes disease is unclear. Nucleocytoplasmic transport, the trafficking of macromolecules between the nucleus and cytoplasm, is tightly regulated by nuclear pore complexes (NPCs) made up of nucleoporins (NUPs). Previous studies offered clues that mHTT may disrupt nucleocytoplasmic transport and a mutation of an NUP can cause HD-like pathology. Therefore, we evaluated the NPC and nucleocytoplasmic transport in multiple models of HD, including mouse and fly models, neurons transfected with mHTT, HD iPSC-derived neurons, and human HD brain regions. These studies revealed severe mislocalization and aggregation of NUPs and defective nucleocytoplasmic transport. HD repeat-associated non-ATG (RAN) translation proteins also disrupted nucleocytoplasmic transport. Additionally, overexpression of NUPs and treatment with drugs that prevent aberrant NUP biology also mitigated this transport defect and neurotoxicity, providing future novel therapy targets.