VEFG/SphK pathway plays an important role in Niemann-Pick type C disease

 

Niemann-Pick type C disease (NP-C) is an lipid metabolism disorder that related to mutations of NPC1 in central nervous system. Previous studies have shown the metabolism disorder led to a storage of sphingosine. In this study, Lee et al. identified the defective of sphingosine kinase (SphK) and vascular endothelial growth factor (VEGF) activities are main signaling that promotes  sphingosine storage. The article was published on Nature Communications.

 

In NP-C patients and NP-C mice, defects of SphK enzyme activity promoted SphK storage level and disease pathogenesis. It has been reported by the author that bone marrow mesenchymal stem cells (BM-MSCs) are able to attenuate symptoms of NP-C mice by restore the sphingolipid disorder in NP-C Purkinje neurons (PNs). Further investigation showed BM-MSC-derived VEGF mediates SphK activity by binding to VEGFR2, leading to an improvement of pathology in NP-C mice PNs and patient-specific cells. Therefore, the VEGF/SphK pathway is a key regulator in keeping sphingolipid balance in PNs. In addition, the disorder caused by inactivation of VEGF/SphK signaling can be corrected by replenishment of VEGF. These results indicates enhancing VEGF signaling is a promising therapeutic strategy for NP-C, via promoting SphK activity.

 

Reference:
Nat Commun. 2014 Nov 24;5:5514.

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