Journal
BRAIN
Volume 143, Issue -, Pages 1073-1087Publisher
OXFORD UNIV PRESS
DOI: 10.1093/brain/awz382
Keywords
HSP; MND; cholesterol; mitochondria; lipidome imbalance
Categories
Funding
- Medical Research Council (MRC) [G1002279]
- Newlife Foundation for Disabled Children
- Wellcome Trust
- Hereditary Spastic Paraplegia Support Group UK
- Halpin Trust
- MRC [G1002279] Funding Source: UKRI
Ask authors/readers for more resources
Motor neuron diseases (MNDs) encompass an extensive and heterogeneous group of upper and/or lower motor neuron degenerative disorders, in which the particular clinical outcomes stem from the specific neuronal component involved in each condition. While mutations in a large number of molecules associated with lipid metabolism are known to be implicated in MNDs, there remains a lack of clarity regarding the key functional pathways involved, and their inter-relationships. This review highlights evidence that defines defects within two specific lipid (cholesterol/oxysterol and phosphatidylethanolamine) biosynthetic cascades as being centrally involved in MND, particularly hereditary spastic paraplegia. We also identify how other MND-associated molecules may impact these cascades, in particular through impaired organellar interfacing, to propose 'subcellular lipidome imbalance' as a likely common pathomolecular theme in MND. Further exploration of this mechanism has the potential to identify new therapeutic targets and management strategies for modulation of disease progression in hereditary spastic paraplegias and other MNDs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available