Abstract
A proper lipid management is paramount for a healthy brain. Lipid homeostasis alterations are known to be causative or risk factors for many neurodegenerative diseases, or key elements in the recovery from nervous system injuries of different etiology. In addition to lipid biogenesis and catabolism, non-enzymatic lipid-binding proteins play an important role in brain function and maintenance through aging. Among these types of lipoproteins, apolipoprotein E has received much attention due to the relationship of particular alleles of its gene with the risk and progression of Alzheimer's disease. However, other lipid-binding proteins whose role in lipid homeostasis and control are less known need to be brought to the attention of both researchers and clinicians. The aim of this review is to cover the knowledge of lipid-managing proteins in the brain, with particular attention to new candidates to be relevant for brain function and health.
Highlights
Multiple sclerosis (MS) and other demyelinating diseases are caused by autoimmune attacks toward myelin components in a pro-inflammatory context associated with blood–brain barrier (BBB) disruption and infiltration of immune system cells
In NiemannPick type C (NPC) patients, cholesterol and other lipids accumulate in late endosomes and lysosomes and are unable to travel to the plasma membrane. These lipid management alterations result in progressive neurodegeneration, starting early in cerebellar Purkinje cells [120], as well as in myelin defects, revealing the importance of cholesterol mobilization from lysosomes, both in neurons and in oligodendrocytes, to form and maintain a functional myelin sheath [121]. Concomitant with this cholesterol dyshomeostasis, genomic instability, and trisomy 21 mosaicism have been described in NPC patients [122], an effect that is thought to be a consequence of changes in membrane fluidity
Lipid-based structures are of high complexity, from apparently simple cell membranes to lipoprotein particles, intracellular lipid droplets, or complex myelin sheaths
Summary
Lipids are on high demand in the brain, since they are required for the long expansions of neurons and, massively, for myelin construction. These structures, characteristic of the nervous system, were initially thought to be static assemblies once development was concluded. Neuronal processes (dendrites and axons), their synaptic terminals, and their myelin sheaths are known to be constantly remodeling. Their reorganization is the basis of experience-dependent plasticity and, importantly, of the unexpected endogenous abilities of our nervous system to recover from damages, disease, and aging-related deterioration. Neurodegenerative diseases as devastating as NiemannPick type C (NPC), where the gene affected codes for a lipid transporter in charge of intracellular
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