The Role of Lipids, Lipid Metabolism and Ectopic Lipid Accumulation in Axon Growth, Regeneration and Repair after CNS Injury and Disease

Cells, 2021 · DOI: https://doi.org/10.3390/cells10051078 · Published: May 1, 2021

Simple Explanation

Axons in the adult mammalian nervous system can extend over formidable distances, up to one meter or more in humans. During development, axonal and dendritic growth requires continuous addition of new membrane. Lipids also serve as energy storage, signaling molecules and they contribute to tissue physiology, as demonstrated by a variety of metabolic disorders in which harmful amounts of lipids accumulate in various tissues through the body. Here, we review the role of lipids, lipid metabolism and ectopic lipid accumulation in axon growth, regeneration and CNS repair. In addition, we outline molecular and pharmacological strategies to ﬁne-tune lipid composition and energy metabolism in neurons and non-neuronal cells that can be exploited to improve neurological recovery after CNS trauma and disease.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Neuronal depletion of lipin 1 promotes axon regeneration after optic nerve injury in mice by regulating glycerolipid metabolism and, more speciﬁcally, triglyceride hydrolysis and phospholipid synthesis.
2
Fatty acid synthesis in satellite glial cells contributes to axon elongation during regeneration of peripheral nerves.
3
Excess accumulation of lipid droplets, particularly cholesteryl esters linked to polyunsaturated fatty acids, in spinal cord astrocytes is associated with cellular stress and inﬂammation.

Research Summary

We have discussed evidence suggesting that reprogramming lipid metabolism, boosting mitochondrial transport and neuron-glia metabolic coupling promote survival and regeneration of injured axons. Not only do such detrimental conditions contribute to axon regeneration failure, but also to insulin resistance, cardiovascular disease and metabolic syndrome, thus leading to poor neurological outcomes and a diminished quality of life. Regaining metabolic control and energy balance may be necessary to promote neuron repair and full body recovery after CNS trauma and disease.

Practical Implications

Therapeutic Lipid Manipulation

Rewiring lipid metabolism can be manipulated for therapeutic gain to favor axon regeneration in both the central and peripheral nervous systems.

Personalized Lipid-Enriched Diets

Personalized lipid-enriched diets may rescue, at least in part, myelination defects.

Metabolic Control

Regaining metabolic control and energy balance may be necessary to promote neuron repair and full body recovery after CNS trauma and disease.

Study Limitations

1
Whether pharmacological and molecular strategies lowering cholesterol synthesis promote neurological recovery after SCI is unknown and deserves further attention in future investigations.
2
Whether mitochondrial transport may be linked to nutrient and energy sensing is not known.
3
The extent to which boosting energy metabolism and mitochondria trafﬁcking may be sufﬁcient to promote functionally relevant regeneration and CNS repair under different experimental conditions awaits conﬁrmation.

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