Therapeutic Role of ELOVL in Neurological Diseases

Abstract

Fatty acids play an important role in controlling the energy balance of mammals. De novo lipogenesis also generates a significant amount of lipids that are endogenously produced in addition to their ingestion. Fatty acid elongation beyond 16 carbons (palmitic acid), which can lead to the production of very long chain fatty acids (VLCFA), can be caused by the rate-limiting condensation process. Seven elongases, ELOVL1–7, have been identified in mammals and each has a unique substrate specificity. Researchers have recently developed a keen interest in the elongation of very long chain fatty acids protein 1 (ELOVL1) enzyme as a potential treatment for a variety of diseases. A number of neurological disorders directly or indirectly related to ELOVL1 involve the elongation of monounsaturated (C20:1 and C22:1) and saturated (C18:0-C26:0) acyl-CoAs. VLCFAs and ELOVL1 have a direct impact on the neurological disease. Other neurological symptoms such as ichthyotic keratoderma, spasticity, and hypomyelination have also been linked to the major enzyme (ELOVL1). Recently, ELOVL1 has also been heavily used to treat a number of diseases. The current review focuses on in-depth unique insights regarding the role of ELOVL1 as a therapeutic target and associated neurological disorders.

Neuroproteomic Analysis after SARS-CoV-2 Infection Reveals Overrepresented Neurodegeneration Pathways and Disrupted Metabolic Pathways

“…The lack of replications of SARS-CoV-2 in the neurons is perhaps due to the decreased expression of ELOVL1 in infected neurons (Figure 2C) as a compensatory mechanism to evade the virus. Furthermore, ELOVL1 deficiency can lead to neurological defects such as hypomyelination [103] that would render the neuronal firing slow and less efficient and, therefore, could explain the fatigue experienced by COVID-19 patients, particularly in long COVID. Our proteomic profiling of infected neurons also revealed downregulation of HMGCS1 (Hydroxy-Methylglutaryl-CoA Synthase), which is involved in cholesterol biosynthesis and was noted to be downregulated in multiple cell lines infected with SARS-CoV-2 [104].…”

Circular RNA HIPK2 Promotes A1 Astrocyte Activation after Spinal Cord Injury through Autophagy and Endoplasmic Reticulum Stress by Modulating miR-124-3p-Mediated Smad2 Repression

“…In astrocytes, Elovl mediates the production of long-chain saturated fatty acids, and Smad2 is associated with autophagy. 60 Therefore, only the following hypothesis is plausible: miR-124-3p/Smad2 axismediated autophagy and/or ER stress play roles in astrocyte activation. We also anticipated validating a hypothesis based on as much literature as possible.…”

“…Since miR-124-3p targets a wide range of molecules, the search was conducted for downstream targets of circHIPK2/miR-124-3p that are involved in the activation of A1 astrocytes. First, by searching the literature, we identified two genes, Elovl and Smad2, that were associated with astrocytes. , Second, studies have shown one mechanism that miR-124-3p inhibits astrocyte activation or switches the astrocytes into induced neurons, wherein autophagy, ER stress, PI3K/AKT/NF-κB, and ARE-mediated mRNA decay signals are considered to be involved. ,, To establish associations among miR-124-3p, astrocyte activation, and potential target genes, we performed a literature review of the study topic. In astrocytes, Elovl mediates the production of long-chain saturated fatty acids, and Smad2 is associated with autophagy .…”

“…First, by searching the literature, we identified two genes, Elovl and Smad2, that were associated with astrocytes. , Second, studies have shown one mechanism that miR-124-3p inhibits astrocyte activation or switches the astrocytes into induced neurons, wherein autophagy, ER stress, PI3K/AKT/NF-κB, and ARE-mediated mRNA decay signals are considered to be involved. ,, To establish associations among miR-124-3p, astrocyte activation, and potential target genes, we performed a literature review of the study topic. In astrocytes, Elovl mediates the production of long-chain saturated fatty acids, and Smad2 is associated with autophagy . Therefore, only the following hypothesis is plausible: miR-124-3p/Smad2 axis-mediated autophagy and/or ER stress play roles in astrocyte activation.…”

“…First, by searching the literature, we identified two genes, Elovl and Smad2, that were associated with astrocytes. 60,61 Second, studies have shown one mechanism that miR-124-3p inhibits astrocyte activation or switches the astrocytes into induced neurons, wherein autophagy, ER stress, PI3K/AKT/NF-κB, and ARE-mediated mRNA decay signals are considered to be involved. 22,24,62 To establish associations among miR-124-3p, astrocyte activation, and potential target genes, we performed a literature review of the study topic.…”