Lipid metabolism alterations in peripheral neuropathies

Abstract

Alterations in lipid metabolism are increasingly recognized as central pathological hallmarks of inherited and acquired peripheral neuropathies. Correct lipid balance is critical for cellular homeostasis. However, the mechanisms linking lipid disturbances to cellular dysfunction and whether these changes are primary drivers or secondary effects of disease remain unresolved. This is particularly relevant in the peripheral nervous system, where the lipid-rich myelin integrity is critical for axonal function, and even subtle perturbations can cause widespread effects. This review explores the role of lipids as structural components as well as signaling molecules, emphasizing their metabolic role in peripheral neurons and Schwann cells. Additionally, we explore the genetic and environmental connections in both inherited and acquired peripheral neuropathies, respectively, which are known to affect lipid metabolism in peripheral neurons or Schwann cells. Overall, we highlight how understanding lipid-centric mechanisms could advance biomarker discovery and therapeutic interventions for peripheral nerve disorders.

Keywords: Charcot-Marie-Tooth disease; Schwann cells; lipid metabolism; lipid rafts; lipid signaling; lipid storage; motor neurons; peripheral neuropathies; sensory neurons.