FAM151B-DT expression is considerably lowered in MAPT mutant neurons and tauopathy brains. Credit score: Molecular Psychiatry (2025). DOI: 10.1038/s41380-025-03277-6
Neurodegenerative ailments, reminiscent of Alzheimer’s illness and dementia, are medical circumstances that entail the progressive lack of neurons and a decline in mind perform. Previous research have discovered a hyperlink between these ailments and the buildup of misfolded proteins, reminiscent of tau and α-synuclein.
Tau is a protein discovered primarily in neurons that sometimes helps to stabilize constructions that transport vitamins and molecules inside neurons, often called microtubules. α-synuclein, however, is a small protein situated on the suggestions of neurons (i.e., pre-synapses), which generally helps to manage the perform of synaptic vesicles, small sacs that launch neurotransmitters throughout synapses.
Whereas these proteins have an vital perform within the wholesome mind, their irregular aggregation has been discovered to be an indicator of a number of neurodegenerative ailments. The molecular processes that immediate their accumulation, nevertheless, haven’t but been totally elucidated.
Researchers at Washington College in St. Louis and College of California not too long ago investigated the position of a newly uncovered RNA molecule, referred to as FAM151B-DT, within the aggregation of tau and α-synuclein proteins. Their findings, revealed in Molecular Psychiatry, recommend that this RNA is a key regulator of protein homeostasis, or in different phrases, that it helps to maintain a steadiness within the manufacturing and degradation of proteins within the mind.
“Neurodegenerative diseases share common features of protein aggregation along with other pleiotropic traits, including shifts in transcriptional patterns, neuroinflammation, disruption in synaptic signaling, mitochondrial dysfunction, oxidative stress, and impaired clearance mechanisms like autophagy,” wrote Arun Renganathan, Miguel A. Minaya and their colleagues of their paper.
“However, key regulators of these pleiotropic traits have yet to be identified. We used transcriptomics, mass spectrometry, and biochemical assays to define the role of a novel lncRNA on tau pathophysiology.”
A beforehand unknown RNA implicated in protein aggregation
As a part of their research, Renganathan and his colleagues examined stem cells and tissue samples utilizing a variety of genetic and experimental instruments. Particularly, they in contrast the degrees of the protein lncRNA in mind tissues derived from people who had been recognized with a neurodegenerative illness to these of people that weren’t.
“We discovered a long non-coding RNA (lncRNA), FAM151B-DT, that is reduced in a stem cell model of frontotemporal lobar dementia with tau inclusions (FTLD-tau) and in brains from FTLD-tau, progressive supranuclear palsy, Alzheimer’s disease, and Parkinson’s disease patients,” wrote Renganathan and their colleagues. “We show that silencing FAM151B-DT in vitro is sufficient to enhance tau and α-synuclein aggregation.”
The researchers grew stem cells within the lab after which silenced the protein that they recognized in these cells. Notably, they discovered that this heightened the aggregation of proteins related to varied neurodegenerative ailments.
“To begin to understand the mechanism by which FAM151B-DT mediates tau aggregation and contributes to several neurodegenerative diseases, we deeply characterized this novel lncRNA and found that FAM151B-DT resides in the cytoplasm where it interacts with tau, α-synuclein,” wrote the authors. “HSC70, and other proteins involved in protein homeostasis. When silenced, FAM151B-DT blocks autophagy, leading to the accumulation of tau and α-synuclein.”
Informing the remedy of neurodegenerative ailments
Total, the outcomes of this current research recommend that the RNA molecule FAM151B-DT is of key significance for the balancing of tau and α-synuclein proteins in cells. Silencing this molecule appears to immediate the undesirable aggregation of proteins linked to neuronal harm and the emergence of neurodegenerative ailments.
The perception gathered by Renganathan and their colleagues might enhance the current understanding of assorted neurodegenerative ailments. Sooner or later, the molecule they recognized might show to be a promising goal for treating these ailments early or addressing a few of their signs.
“Importantly, we discovered that increasing FAM151B-DT expression is sufficient to promote autophagic clearance of phosphorylated tau and α-synuclein, and reduce tau and α-synuclein aggregation,” wrote the authors. “Overall, these findings pave the way for further exploration of FAM151B-DT as a promising molecular target for several neurodegenerative diseases.”
Written for you by our writer Ingrid Fadelli, edited by Gaby Clark, and fact-checked and reviewed by Robert Egan—this text is the results of cautious human work. We depend on readers such as you to maintain impartial science journalism alive.
If this reporting issues to you,
please think about a donation (particularly month-to-month).
You will get an ad-free account as a thank-you.
Extra data:
Arun Renganathan et al, A novel lncRNA FAM151B-DT regulates degradation of aggregation inclined proteins, Molecular Psychiatry (2025). DOI: 10.1038/s41380-025-03277-6.
© 2025 Science X Community
Quotation:
Newly found RNA molecule might restrict protein aggregation and stop neuronal harm (2025, November 12)
retrieved 12 November 2025
from https://medicalxpress.com/information/2025-11-newly-rna-molecule-limit-protein.html
This doc is topic to copyright. Other than any honest dealing for the aim of personal research or analysis, no
half could also be reproduced with out the written permission. The content material is supplied for data functions solely.
