08 Apr Hebrew University Study Finds Potential Blood Marker of Pre-Symptomatic Parkinson’s Disease

MedicalResearch.com Interview with:

Hermona Soreq, lab, students, collaboration

Prof. Hermona Soreq
The Edmond and Lily Safra Center for Brain Sciences (ELSC) and
The Alexander Silberman Institute of Life Science
at the Hebrew University

MedicalResearch.com: What is the background for this study? What are tRFs and how do they impact neurodegeneration?

Response:   tRFs: The molecular SOS of early life stress

If you remember your high school biology classes, you might remember that tRNAs are molecules that help assemble proteins based on encoding amino acids. In recent years, scientists discovered that when these molecules break down it’s not merely cellular garbage – it can be gold. Specifically, tRNAs can be sliced into short pieces, called tRNA fragments (or tRFs), which act like little regulators, switching translation on and off in ways we’re still trying to understand.

Think of a tRNA as a Swiss army knife. It has structure, function, and folds on itself. But under certain conditions – like stress – it’s chopped up into smaller pieces, each with a distinct signal. These fragments aren’t random junk; they’re more like emergency messages, scattered through the bloodstream, reflecting the body’s internal state.

That idea – of tRFs as biological SOS signals – led us to wonder: could these fragments tell us what the fetus experiences in utero? Could they show us, in molecular form, the impact of maternal psychosocial stress?

MedicalResearch.com: Are they associated with any other neurodegenerative causes?

Response:   Yes, Alzheimer’s disease and Parkinson’s disease.

MedicalResearch.com: What are the main findings?

Response:  Our team collected blood samples from mother-newborn dyads at a hospital in Munich. The mothers filled out standardized stress questionnaires during pregnancy, allowing us to classify them into “stressed” or “control” groups based on their perceived stress levels.

Then at birth, we looked into both maternal and umbilical cord serum. Why serum? It’s routinely collected, contains information on various states, and crucially – it’s enriched with these tiny RNA messengers.

We used small-RNA sequencing to profile the RNA contents, focusing on the newborns first. The goal wasn’t just to identify individual tRFs, but to look at families of tRFs – grouped by origin (nuclear vs mitochondrial), parental tRNA coded amino acid, and their specific cleavage type.

Here’s where the story gets surprising.

Mothers whisper, babies shout

While mothers’ serum showed almost no significant change in tRFs, their babies’ samples told a much louder story.

We found that newborns of stressed mothers had significantly altered tRF profiles—and the changes weren’t random. Entire families of mitochondrial tRFs were reduced, particularly in female newborns. These were not one-off molecules, but coordinated shifts in groups of RNAs, acting like a biological choir singing a different tune to the signals of prenatal stress.

Meanwhile, male newborns responded differently. Their standout change wasn’t in tRFs, but in acetylcholinesterase activity – an enzyme that breaks down acetylcholine, a neurotransmitter tied to stress, cognitive processes, and inflammation regulation. Males showed elevated levels, suggesting their bodies may be ramping up to shut down cholinergic signaling after stress—potentially making them more vulnerable. In contrast, female newborns reacted to their mothers’ stress experiences far more effectively.

We felt like we stumbled upon a core sex-specific stress pathway unfold – while both male and female newborns showed both effects, the females showed stronger tRF responses suggesting more effective gene expression regulation, whereas male newborns showed stronger cholinesterase response suggesting stronger protein activities.

MedicalResearch.com: What should readers take away from your report?

Response:   A key innovation in our analysis was to stop treating tRFs like isolated molecules and start grouping them by shared characteristics. It’s a bit like analyzing a symphony: individual notes matter, but the patterns within entire sections – the strings, the woodwinds—reveal the deeper structure.

We found that these group patterns carry more information than any one fragment alone, influencing not just expression but also length. And they vary with sex, stress, and even between mother and her baby.

This approach could reshape how we analyse tRFs in biological systems. It’s not just about the solos -it’s about the harmonies.

Citation:

The research paper titled “Pre-symptomatic Parkinson’s disease blood test quantifying repetitive sequence motifs in transfer RNA fragments” is now available in Aging Nature and can be accessed at https://www.nature.com/articles/s43587-025-00851-z (DOI-10.1038/s43587-025-00851-z).

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Last Updated on April 11, 2025 by Marie Benz MD FAAD