Conserved pharmacological rescue of XXXX -related phenotypes across model organisms.

@entity1 @entity9718 @entity2199 @entity12408 @entity8074 @entity6693 @entity898 @entity3392 @entity179 @entity72046 @entity426 @entity717 @entity238
UNASSIGNED: @entity9718 ( @entity9718 ) are a group of @entity179 causing progressive @entity426 . Over 50 genes have now been associated with HSP. Despite the recent explosion in genetic knowledge, HSP remains without pharmacological treatment. Loss-of-function mutation of the @entity12408 gene, also known as @entity12408 , is the most common cause of HSP in @entity1 . @entity12408 is conserved across animal species and regulates microtubule dynamics. Recent studies have shown that it also modulates endoplasmic reticulum (ER) stress. Here, utilizing null @entity12408 homologues in @entity2199 , @entity238 , and @entity3392 , we tested FDA approved compounds known to modulate ER stress in order to ameliorate locomotor phenotypes associated with HSP. We found that @entity717 found in all of our spastin models could be partially rescued by @entity72046 , @entity6693 , @entity898 , @entity8074 and salubrinal. In addition, we show that established biomarkers of ER stress levels correlated with improved locomotor activity upon treatment across model organisms. Our results provide insights into biomarkers and novel therapeutic avenues for HSP.
