LncRNA MEG8 ameliorates Parkinson's disease neuro-inflammation through miR-485-3p/FBXO45 axis

Xia Lin1, Taotao Tao1, Xinwei He1

  • 1Department of Neurology, Taizhou Central Hospital (Taizhou University Hospital), No.999, Donghai Avenue, Jiaojiang District, Taizhou, 318000, Zhejiang, China.

Acta Neurologica Belgica
|October 9, 2023
PubMed
Abstract

Insights

Long non-coding RNA maternally expressed 8 (MEG8) shows potential as a diagnostic biomarker for Parkinson's disease (PD). Elevated MEG8 may reduce inflammation in PD by regulating the miR-485-3p/FBXO45 pathway.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Long non-coding RNA maternally expressed 8 (MEG8) is implicated in inflammatory regulation.
  • The role and mechanisms of MEG8 in Parkinson's disease (PD) remain uncharacterized.
  • This study investigates the clinical significance and biological function of MEG8 in PD.

Purpose of the Study:

  • To evaluate MEG8 as a diagnostic biomarker for Parkinson's disease (PD).
  • To elucidate the biological function and underlying mechanisms of MEG8 in PD pathogenesis.
  • To explore the potential of MEG8 in mitigating inflammatory responses associated with PD.

Main Methods:

  • Serum and cellular levels of MEG8, miR-485-3p, and FBXO45 were quantified using RT-qPCR in 102 PD patients, 86 AD patients, and 80 healthy controls.
  • An in vitro model of LPS-induced microglia BV2 cells was utilized to study inflammatory responses.
  • Diagnostic value was assessed via ROC curve analysis, and targeting relationships were validated using dual-luciferase reporter and RIP assays.

Main Results:

  • MEG8 and FBXO45 levels were significantly decreased in PD patients and LPS-treated BV2 cells, while miR-485-3p levels were elevated.
  • Serum MEG8 demonstrated high sensitivity and specificity for distinguishing PD patients from healthy and AD controls.
  • MEG8 alleviated LPS-induced inflammation, an effect dependent on the miR-485-3p/FBXO45 axis, where MEG8 acts as a sponge for miR-485-3p, inhibiting it and promoting FBXO45 expression.

Conclusions:

  • Elevated MEG8 serves as a potential diagnostic biomarker for Parkinson's disease (PD).
  • MEG8 may exert anti-inflammatory effects in PD through the miR-485-3p/FBXO45 pathway.
  • The findings highlight a novel molecular mechanism involving MEG8 in PD pathophysiology.

Related Concept Videos

Parkinson's Disease: Treatment01:24

Parkinson's Disease: Treatment

Neurodegenerative disorders, such as Parkinson's Disease (PD), involve the gradual and irreversible destruction of neurons in particular brain areas. These disorders exhibit standard features like proteinopathies, selective vulnerability of some neurons, and an interaction of intrinsic properties, genetics, and environmental influences in neural injury.
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
283
Neural Regulation01:37

Neural Regulation

Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
39.5K
Parkinson's Disease: Overview01:15

Parkinson's Disease: Overview

Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
579
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.0K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.6K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.5K