A strand of hope: small RNAs could be biomarkers for neurodegenerative diseases

Scientists from the Italian Institute of Technology in Genoa, Italy, have discovered that decreased levels of an RNA molecule called piRNA in the brain could make it difficult to generate new neurons. This reduces the number of neurons in the brain, thus causing neurodegenerative diseases and cognitive impairment in aged individuals. 

The study published in the journal EMBO Reports opens a way to diagnose neurodegenerative diseases like Alzheimer’s and Parkinson’s at an early stage.  

Looking at the roots 

RNA is a single strand of genetic material abundantly found in cells. When a protein must be made, the blueprint from the DNA is transferred to a type of RNA called messenger RNA (mRNA), also known as coding RNA. These coding RNAs swim to the protein manufacturing unit of the cells, where they make the required proteins.   

Non-coding RNA helps transfer the mRNA molecule to the protein manufacturing unit. An example of non-coding RNA is transfer RNA (tRNA). Non-coding RNA is an unstable molecule constantly searching for enzymes and other proteins to stabilise. 

“We know that these non-coding RNAs are particularly abundant in the brain, but we just started to appreciate the role of many non-coding RNA in the brain function and in disease,” says Davide De Pietri Tonelli, senior researcher from the miRNA laboratory at the Italian Institute of Technology, Italy. 

Previous studies have identified that non-coding RNA plays an essential role in the brain in neural processes. However, the exact mechanisms were unclear. The current research throws light on the same. 

Tonelli adds that non-coding RNA holds promise for translational applications (can be applied for health improvement). However, there is still a huge mechanistic gap to be filled in basic research. 

The team found that when a non-coding RNA interacts with a specific protein called piwi protein, it stabilises to piwi-RNA or piRNA. The protein piwi is mainly found in male reproductive cells and the neural stem cells of the hippocampus region in the brain.  

Read more: Know the brain regions 

Studies showed that piRNA is found in the hippocampus. It helps young cells grow into mature cells with specified functions by a process called cell differentiation.  

Based on such studies, researchers hypothesised that the piRNA could be involved in neurogenesis- a process of neuron formation in the hippocampus region.  

Less piwi, fewer neurons 

The researchers experimented on mice by dividing them into three groups: young mice, aged mice with cognitive impairment, and mice where the activity of piwi protein is switched off (piwi-knock-out mice). 

On scrutinising the piRNA activity in them using advanced screening methods, the researchers found that the young mice group had healthy neurons, while the aged mice group had a limited number of neurons due to reduced levels of piRNA. This corresponded with known studies indicating that the quantity and activity of piwi protein diminished with age. However, in piwi-knock-out mice, there was no piRNA production, thus reducing the neurogenesis. These decreasing levels of piRNA caused cognitive impairment and toxin build-up in the brain leading to neurodegenerative disorders.  

“This study provides evidence for the role of piRNA in maintaining healthy cognitive functions and preventing ageing-related brain diseases,” says Tonelli. In addition, it opens new avenues for therapy as it allows for early diagnosis of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, he adds. 

Read more: Decoding the genetics of Alzheimer’s: the role of APOE4 and SHMOOSE 

In the future, Tonelli’s team plans to study piRNA biology on various models of neuronal disease, thus possibly validating them as biomarkers for early diagnosis.