Motor neuron diseases (MNDs) are characterized by selective death of motor 
neurons and include mainly adult-onset amyotrophic lateral sclerosis (ALS) and 
spinal muscular atrophy (SMA). Neurodegeneration is not the single pathogenic 
event occurring during disease progression. There are multiple lines of evidence 
for the existence of defects in lipid metabolism at peripheral level. For 
instance, hypermetabolism is well characterized in ALS, and dyslipidemia 
correlates with better prognosis in patients. Lipid metabolism plays also a role 
in other MNDs. In SMA, misuse of lipids as energetic nutrients is described in 
patients and in related animal models. The composition of structural lipids in 
the central nervous system is modified, with repercussion on membrane fluidity 
and on cell signaling mediated by bioactive lipids. Here, we review the main 
epidemiologic and mechanistic findings that link alterations of lipid metabolism 
and motor neuron degeneration, and we discuss the rationale of targeting these 
modifications for therapeutic management of MNDs.