Figure 7.

Dysregulated lipid metabolism exerts a multifaceted effect on neurons in ALS. Dysregulation of neuronal lipid metabolism in ALS impacts energy use, structural integrity and signaling processes. Increased use of lipid as an energy substrate leads to increased oxidative stress. This exacerbates inflammation, mitochondrial dysfunction, metabolic dysfunction and excitotoxicity. Altered lipid metabolism also disrupts intracellular lipids leading to cytoskeletal defects and the denervation of neuromuscular junctions. Finally, changes in lipid metabolism impacts the composition of lipid rafts. This disrupts signaling processes that are crucial in regulating neurotransmitter synthesis and release, cytoskeletal integrity and intracellular transport.