Lipid alterations in hereditary peripheral neuropathies: common mechanisms in disease heterogeneity?

While the impact of lipid alterations on central nervous system disorders is well-studied, increasing evidence indicates that lipids also play an important role in the pathology of hereditary peripheral neuropathies (HPN). It is becoming clear that Schwann cells and neurons in peripheral nerves heavily depend on lipids for membrane interactions, (sub)cellular signalling, and the formation of myelin sheaths. In support of this notion, disturbances in the level and composition of lipid classes, including phospholipids, sphingolipids and cholesterol, perturb normal functioning of peripheral nerves. Intriguingly, lipid disturbances seem to be a common denominator within the heterogeneous group of HPN, with hindrances in cholesterol and sphingolipid metabolism primarily influencing Schwann cell and neuron homeostasis, respectively. In this review, we provide an overview of lipid disturbances in various HPN with the goal of finding main commonalities between the different diseases and to identify potential novel treatment strategies.