Models of TDP-43 Proteinopathy in ALS / FTD and RNA targeting using CRISPR / Cas9

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" Models of TDP-43 Proteinopathy in ALS / FTD and RNA targeting using CRISPR / Cas9 "
Pirie, Elaine Christine Ravits, John MYeo, Eugene W

Document Type	:	Latin Dissertation
Language of Document	:	English
Record Number	:	897443
Doc. No	:	TL35k1q39z
Main Entry	:	Shrodes, Addie C.
Title & Author	:	Models of TDP-43 Proteinopathy in ALS / FTD and RNA targeting using CRISPR / Cas9\ Pirie, Elaine ChristineRavits, John MYeo, Eugene W
Date	:	2017
student score	:	2017
Abstract	:	Misregulation of RNA processing is a major component of the related neurodegenerative diseases Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. TDP-43 is an RNA binding protein and the primary pathological finding in both diseases. Post-translational modification of TDP-43 by direct S-nitrosylation of cysteines 173 and 175 leads to disulfide bond formation and loss of solubility in ALS / FTD models. Further, TDP-43 aggregation may be able to induce nitrosative stress within the cell, leading to further loss of solubility. We present models of TDP-43 aggregation that demonstrate TDP-43 is capable of propagating between cells quantifiably, spreading disease-associated aggregates. C9orf72 is the most common genetic cause of ALS / FTD, and here we establish a CRISPR / Cas9 technology capable of tracking and degrading RNA foci found in in myotonic dystrophy and C9 ALS. Our findings provide a novel framework for therapeutics targeted at TDP-43 aggregation and RNA toxicity.
Added Entry	:	Pirie, Elaine Christine
Added Entry	:	UC San Diego