A GJA1 Variant Triggers Earlier SPG4 Onset by Destabilizing Deubiquitinase VCPIP1 to Lower SPASTIN Levels.

Key Points

• This research aims to explore how the GJA1 R148Q variant affects the onset of SPG4 by interacting with VCPIP1 and SPASTIN levels.
• Analysis of GJA1 variant effects on VCPIP1 stability
• Assessment of SPASTIN expression levels
• Investigation of GJA1-VCPIP1-SPASTIN signaling interactions
• GJA1 R148Q variant destabilizes VCPIP1 leading to lower SPASTIN levels
• The variant triggers earlier onset of SPG4 symptoms
• Potential identification of a therapeutic axis targeting GJA1 and SPASTIN for SPG4 treatment