MicroRNA-128a Dysregulation in Transgenic Huntington's Disease Monkeys

Overview

Journal Mol Brain

Publisher Biomed Central

Specialties Molecular Biology
Neurology

Date 2014 Jun 16

PMID 24929669

Citations 43

Authors

Jannet Kocerha

Yan Xu

Melinda S Prucha

Dongming Zhao

Anthony W S Chan

Affiliations

Soon will be listed here.

Abstract

Background: Huntington's Disease (HD) is a progressive neurodegenerative disorder with a single causal mutation in the Huntingtin (HTT) gene. MicroRNAs (miRNAs) have recently been implicated as epigenetic regulators of neurological disorders, however, their role in HD pathogenesis is not well defined. Here we study transgenic HD monkeys (HD monkeys) to examine miRNA dysregulation in a primate model of the disease.

Results: In this report, 11 miRNAs were found to be significantly associated (P value < 0.05) with HD in the frontal cortex of the HD monkeys. We further focused on one of those candidates, miR-128a, due to the corresponding disruption in humans and mice with HD as well as its intriguing lists of gene targets. miR-128a was downregulated in our HD monkey model by the time of birth. We then confirmed that miR-128a was also downregulated in the brains of pre-symptomatic and post-symptomatic HD patients. Additionally, our studies confirmed a panel of canonical HD signaling genes regulated by miR-128a, including HTT and Huntingtin Interaction Protein 1 (HIP1).

Conclusion: Our studies found that miR-128a may play a critical role in HD and could be a viable candidate as a therapeutic or biomarker of the disease.

Citing Articles

The Role of MicroRNAs in Neurodegeneration: Insights from Huntington's Disease.

Mansour R, Shaker A, Abulsoud A, Mageed S, Ashraf A, Elsakka E Mol Neurobiol. 2025; .

PMID: 40009259 DOI: 10.1007/s12035-025-04750-7.

RNA dysregulation in neurodegenerative diseases.

Li Y, Sun S EMBO J. 2025; 44(3):613-638.

PMID: 39789319 PMC: 11790913. DOI: 10.1038/s44318-024-00352-6.

The Role of miR-128 in Neurodegenerative Diseases.

Lanza M, Cuzzocrea S, Oddo S, Esposito E, Casili G Int J Mol Sci. 2023; 24(7).

PMID: 37046996 PMC: 10093830. DOI: 10.3390/ijms24076024.

The updated development of blood-based biomarkers for Huntington's disease.

Zhang S, Cheng Y, Shang H J Neurol. 2023; 270(5):2483-2503.

PMID: 36692635 PMC: 9873222. DOI: 10.1007/s00415-023-11572-x.

Non-coding RNAs in human health and disease: potential function as biomarkers and therapeutic targets.

Loganathan T, C G Funct Integr Genomics. 2023; 23(1):33.

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