Repository logo
 

Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington's disease

Published version
Peer-reviewed

Type

Article

Change log

Authors

Di Pardo, A 
Amico, E 
Basit, A 
Armirotti, A 
Joshi, P 

Abstract

Huntington's disease is characterized by a complex and heterogeneous pathogenic profile. Studies have shown that disturbance in lipid homeostasis may represent a critical determinant in the progression of several neurodegenerative disorders. The recognition of perturbed lipid metabolism is only recently becoming evident in HD. In order to provide more insight into the nature of such a perturbation and into the effect its modulation may have in HD pathology, we investigated the metabolism of Sphingosine-1-phosphate (S1P), one of the most important bioactive lipids, in both animal models and patient samples. Here, we demonstrated that S1P metabolism is significantly disrupted in HD even at early stage of the disease and importantly, we revealed that such a dysfunction represents a common denominator among multiple disease models ranging from cells to humans through mouse models. Interestingly, the in vitro anti-apoptotic and the pro-survival actions seen after modulation of S1P-metabolizing enzymes allows this axis to emerge as a new druggable target and unfolds its promising therapeutic potential for the development of more effective and targeted interventions against this incurable condition.

Description

Keywords

Aged, Aldehyde-Lyases, Animals, Disease Models, Animal, Enzyme Inhibitors, Gene Expression Regulation, Humans, Huntington Disease, Lysophospholipids, Male, Mice, Molecular Targeted Therapy, Phosphotransferases (Alcohol Group Acceptor), Receptors, Lysosphingolipid, Sphingosine

Journal Title

Scientific Reports

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

7

Publisher

Nature Publishing Group
Sponsorship
Parkinson's UK (via Newcastle University) (RES/0168/7579)