Vital role of lipids in upper motor neurons

Implications for HSP and its treatment

Dr Hande Ozdinler

This important, wide-ranging review of the role of lipids, especially in upper motor neurons, covers multiple aspects of their involvement in maintaining the health of the cells, and the multiple mechanisms of impairment when the lipid balance is disrupted in neuromuscular diseases.

The review discusses the relationship between the known HSP genes and the lipids involved; drug, diet and gene based treatments in relation to lipids; and the potential for lipid biomarkers of disease.

The review was headed by Dr Hande Ozdinler and her team in the Ozdinler lab at Northwestern University in Chicago, a leading centre for research into neurodegeneration.


Building evidence reveals the importance of maintaining lipid homeostasis for the health and function of neurons, and upper motor neurons (UMNs) are no exception. UMNs are critically important for the initiation and modulation of voluntary movement as they are responsible for conveying cerebral cortex’ input to spinal cord targets.

To maintain their unique cytoarchitecture with a prominent apical dendrite and a very long axon, UMNs require a stable cell membrane, a lipid bilayer. Lipids can act as building blocks for many biomolecules, and they also contribute to the production of energy. Therefore, UMNs require sustained control over the production, utilization and homeostasis of lipids.

Perturbations of lipid homeostasis lead to UMN vulnerability and progressive degeneration in diseases such as hereditary spastic paraplegia (HSP) and primary lateral sclerosis (PLS). Here, we discuss the importance of lipids, especially for UMNs.

SOURCE: Semin Cell Dev Biol. 2020 Dec 13;S1084-9521(20)30004-5. doi: 10.1016/j.semcdb.2020.11.004. Online ahead of print. PMID: 33323321 Copyright © 2020 Elsevier Ltd. All rights reserved.

Importance of lipids for upper motor neuron health and disease

Aksu Gunay  1 Heather H Shin  1 Oge Gozutok  1 Mukesh Gautam  1 P Hande Ozdinler  2

  1. Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA, 60611.
  2. Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA, 60611.

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