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Can microRNA solve a big AD problem?
BLOOMINGTON, Ind.—In life, both in terms of things pleasant and unpleasant, it’s often the “little things” that make a difference, that pile up in good or bad ways, that are just so sweet (or terrible) that they really stand out in an otherwise banal day. Well, at Indiana University (IU), the “little things” in this case are microRNAs—those small non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression. And this “little thing” might spell happy news for neurodegenerative disease screening.
Because what the IU researchers found was early evidence that the tiny snippets of genetic material called microRNA may help with early detection of conditions such as Alzheimer’s disease. In a study titled “Presymptomatic change in microRNAs modulates Tau pathology” and published June 18 in Nature Scientific Reports, they found that changes in microRNA are detectable in mice long before they start to show symptoms from neurodegeneration. These microRNA changes, they say, provide a potential biomarker for various neurological conditions and provide an early diagnostic warning sign—as well as making it easier to draw a roadmap when treating the disease and researching its etiology and response to therapy for future treatments.
“Identifying biomarkers early in a disease is important for diagnosing the condition, and following its progression and response to treatment,” stated Hui-Chen Lu, a professor in the Linda and Jack Gill Center for Biomolecular Science and the Department of Psychological and Brain Sciences, a part of the IU Bloomington College of Arts and Sciences, who led the study. “You need something that can predict your future.”
There is currently no treatment to stop or reverse the effects of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis or Huntington’s disease. It’s also estimated that Alzheimer’s disease alone, which is the most common of these disorders, will affect 14 million Americans and cost taxpayers $1.1 trillion by 2050.
Unlike regular “messenger RNA,” which direct cells to produce specific proteins, microRNA plays a regulatory role, increasing or decreasing the number of proteins that messenger RNAs encode, the IU researchers explain. A single snippet of microRNA can impact the function of tens or hundreds of proteins in the body.
Due to their stability in urine and blood, there is growing interest in using microRNA as biomarkers for disease prediction and diagnosis. Lu’s study is an early step to learn whether microRNA can be used to detect neurodegenerative disorders.
To explore this question, Lu and colleagues analyzed microRNA and messenger RNA in two groups: a healthy group and a group genetically modified to develop symptoms of dementia. The team found the highest level of dysregulation in the microRNA of the dementia group before their physical symptoms developed.
“Higher levels of pre-symptomatic microRNA dysregulation are significant because it strongly suggests that it may have a role in changes in the brain in later stages,” Lu said.
The team then compared the microRNA changes to the messenger RNA changes to identify biological pathways affected by microRNA dysregulation. Their analysis suggested that changes in microRNA affected pathways related to immunity in the dementia-prone model.
In response, the team then conducted additional tests to study a specific type of microRNA that was elevated in the dementia model. The microRNA—called microRNA 142—is known to play a major role in inflammation, a part of the immune response. They found that introducing this microRNA into the brain triggered a significant neuroinflammation. The result is important since many other studies have shown that chronic inflammation contributes to many types of disease, including neurodegeneration, Lu said.
She added that the next step will be to learn whether microRNA 142 is easily detectable through a blood test, a key quality for a truly non-invasive biomarker.
As notable as the finding is, of course, the IU researchers are far from alone in looking at microRNAs and neurodegeneration, including Alzheimer’s disease (AD). In fact, earlier this year, also in Nature Scientific Reports, in a paper titled “Analysis of microRNA and Gene Expression Profiles in Alzheimer’s Disease: A Meta-Analysis Approach,” a research team noted: “[M]olecular study of AD could have an important role in detecting genes involved in the disease. On the other hand, a variety of researchers showed that miRNAs and expression of target genes were tightly associated with molecular events in neurodegenerative diseases such as AD4. The miRNAs in the central nervous system have been shown that contributes to the regulation of development, survival, function, and plasticity20. Moreover, any disruption and alterations in microRNAs and their expression in neurons, leading to neurodegenerative diseases such as Alzheimer’s disease (AD)20. It is noteworthy that miRNAs have a high abundance in the central nervous system, and mostly their expression patterns are brain-specific21. According to our results, the DEGs and DEmiRs both can be a potential candidate for biomarkers in AD. Other studies such as qRT-PCR can also be suggested for confirming them.”