DDX3X overexpression decreases dipeptide repeat proteins in a mouse model of C9ORF72-ALS/FTD

In this study, we examined the in vivo efficacy of DDX3X overexpression using a mouse model. We expressed exogenous DDX3X or GFP in the central nervous system (CNS) of the C9-500 ALS/FTD BAC transgenic or non-transgenic control mice using adeno-associated virus serotype 9 (AAV9). The DPR levels were significantly reduced in the brains of DDX3X-expressing C9-BAC mice compared to the GFP control even twelve months after virus delivery. Additionally, p62 aggregation was also decreased. No neuronal loss or neuroinflammatory response were detected in the DDX3X overexpressing C9-BAC mice. This work demonstrates that DDX3X overexpression effectively reduces DPR levels in vivo without provoking neuroinflammation or neurotoxicity, suggesting the potential of increasing DDX3X expression as a therapeutic strategy for C9ORF72-ALS/FTD.PMID:38556190 | DOI:10.1016/j.expneurol.2024.114768

Source: Experimental Neurology - March 31, 2024 Category: Neurology Authors: Xiujuan Fu Zhe Zhang Lindsey R Hayes Noelle Wright Julie Asbury Shelley Li Yingzhi Ye Shuying Sun Source Type: research