Neurodegenerative disease-associated microRNAs acting as signaling molecules modulate CNS neuron structure and viability DOI Creative Commons
Victor Kumbol, Andranik Ivanov, Hugo McGurran

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 24, 2025

Abstract Background Dysregulation of microRNA (miRNA) expression in the brain is a common feature neurodegenerative diseases. Beyond their conventional role regulating gene at post-transcriptional level, certain miRNAs can act extracellularly as signaling molecules. Our study elucidates identity such miRNA species serving ligands for membrane receptors expressed central nervous system (CNS) neurons and impact on context disease. Methods We combined machine learning approach with analysis disease-associated databases to predict Alzheimer’s disease (AD)-associated potential molecules single-stranded RNA-sensing Toll-like (TLRs) 7 8. TLR-expressing HEK-Blue reporter cells, primary murine microglia, human THP-1 macrophages were used validate AD mouse TLR7 and/or TLR8. Interaction between cortical applied was analyzed by live cell imaging confocal microscopy. Transcriptome changes exposed assessed RNAseq RT-qPCR. The extracellular miRNAs’ effects CNS neuron structure investigated cultures iPSC-derived immunocytochemistry. employed model intrathecal injection assess acting vivo. Results identified AD-associated miR-124-5p, miR-92a-1-5p, miR-9-5p, miR-501-3p novel endogenous These being stable active taken up via endocytosis induced neuronal inflammation-, proliferation-, apoptosis-related expression. Exposure both led alterations dendrite axon structure, synapse protein expression, viability sequence-dependent fashion. Extracellular introduction into cerebrospinal fluid mice resulted synapses, loss cerebral cortex. Most observed miRNA-induced involved TLR7/8 signaling. Conclusion Neurodegenerative form including neurons, thereby modulating viability.

Language: Английский

Amyloid-β-Induced Neurotoxicity Modulates miR-98 and miR-200 Expression in SH-SY5Y Cells: A Step Toward Alzheimer’s Biomarker Discovery DOI Creative Commons
Ezgi Keske, Ayyub Ebrahimi, Özlem Sağlam-Uçar

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by abnormal protein accumulation, with no effective, non-invasive early diagnostic tools currently available. MicroRNAs (miRNAs), essential for neuronal survival and function, have been implicated in AD neuropathology. This study investigates the potential of miRNAs as biomarkers assessing expression levels relevant to amyloid toxicity. An model was developed SH-SY5Y human neuroblastoma cells adequate Aβ42 analyze involvement diagnosis. ELISA, MTT assays, Congo red staining were utilized quantify qualitative quantitative formation. The related genes, particularly those targeting APP β-secretase, measured using real-time PCR. Amyloid toxicity successfully induced, an increase significant changes genes targeted observed. Specifically, it observed that miR-200a upregulated miR-98 down-regulated treated cells. Notably, altered patterns these showed strong correlation pathological markers AD, suggesting their indicators. Our findings enhance our understanding mechanisms offer insights into Detecting preclinical stages may enable earlier symptomatic intervention. In particular, dysregulation certain play role processes such plaque formation AD. respond neurotoxic stimuli can be identified vitro models confirmed vivo studies. These studies will help us understand both development noninvasive tests therapeutic approaches miRNAs.

Language: Английский

Citations

0
Neurodegenerative disease-associated microRNAs acting as signaling molecules modulate CNS neuron structure and viability DOI Creative Commons
Victor Kumbol, Andranik Ivanov, Hugo McGurran

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 24, 2025

Abstract Background Dysregulation of microRNA (miRNA) expression in the brain is a common feature neurodegenerative diseases. Beyond their conventional role regulating gene at post-transcriptional level, certain miRNAs can act extracellularly as signaling molecules. Our study elucidates identity such miRNA species serving ligands for membrane receptors expressed central nervous system (CNS) neurons and impact on context disease. Methods We combined machine learning approach with analysis disease-associated databases to predict Alzheimer’s disease (AD)-associated potential molecules single-stranded RNA-sensing Toll-like (TLRs) 7 8. TLR-expressing HEK-Blue reporter cells, primary murine microglia, human THP-1 macrophages were used validate AD mouse TLR7 and/or TLR8. Interaction between cortical applied was analyzed by live cell imaging confocal microscopy. Transcriptome changes exposed assessed RNAseq RT-qPCR. The extracellular miRNAs’ effects CNS neuron structure investigated cultures iPSC-derived immunocytochemistry. employed model intrathecal injection assess acting vivo. Results identified AD-associated miR-124-5p, miR-92a-1-5p, miR-9-5p, miR-501-3p novel endogenous These being stable active taken up via endocytosis induced neuronal inflammation-, proliferation-, apoptosis-related expression. Exposure both led alterations dendrite axon structure, synapse protein expression, viability sequence-dependent fashion. Extracellular introduction into cerebrospinal fluid mice resulted synapses, loss cerebral cortex. Most observed miRNA-induced involved TLR7/8 signaling. Conclusion Neurodegenerative form including neurons, thereby modulating viability.

Language: Английский

Citations

0