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Neurobiol Dis. 2014 Dec;72 Pt A:48-53. doi: 10.1016/j.nbd.2014.05.034. Epub 2014 Jun 5.

MicroRNAs: a connection between cholesterol metabolism and neurodegeneration.

Author information

1
Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Integrative Cell Signaling and Neurobiology of Metabolism Program, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Medicine, New York University School of Medicine, New York, NY, USA.
2
Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Integrative Cell Signaling and Neurobiology of Metabolism Program, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA. Electronic address: carlos.fernandez@yale.edu.

Abstract

Dysregulation of cholesterol metabolism in the brain has been associated with many neurodegenerative disorders such as Alzheimer's disease, Niemann-Pick type C disease, Smith-Lemli-Opitz syndrome, Hungtington's disease and Parkinson's disease. Specifically, genes involved in cholesterol biosynthesis (24-dehydrocholesterol reductase, DHCR24) and cholesterol efflux (ATP-binding cassete transporter, ABCA1, and apolipoprotein E, APOE) have been associated with developing Alzheimer's disease. Indeed, APOE was the first gene variation found to increase the risk of Alzheimer's disease and remains the risk gene with the greatest known impact. Mutations in another cholesterol biosynthetic gene, 7-dehydrocholesterol reductase (DHCR7), cause Smith-Lemli-Opitz syndrome and impairment in cellular cholesterol trafficking caused by mutations in the NPC1 protein results in Niemann-Pick type C disease. Taken together, these findings provide strong evidence that cholesterol metabolism needs to be controlled at very tight levels in the brain. Recent studies have implicated microRNAs (miRNAs) as novel regulators of cholesterol metabolism in several tissues. These small non-coding RNAs regulate gene expression at the post-transcriptional level by either suppressing translation or inducing mRNA degradation. This review article focuses on how cholesterol homeostasis is regulated by miRNAs and their potential implication in several neurodegenerative disorders, such as Alzheimer's disease. Finally, we also discuss how antagonizing miRNA expression could be a potential therapy for treating cholesterol related diseases.

KEYWORDS:

Cholesterol metabolism; Neurodegenerative disorders; miRNAs

PMID:
24907491
PMCID:
PMC4252369
DOI:
10.1016/j.nbd.2014.05.034
[Indexed for MEDLINE]
Free PMC Article

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