Biology subjects

Sanadgol, N.

Publications and source records attributed to Sanadgol, N..

2 recordsLinked to original sources

bioRxiv2025

Deciphering the circular RNAs landscape in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons, with most cases lacking a clear genetic basis. Emerging evidence highlights the involvement of non-coding RNAs, particularly circular RNAs (circRNAs), in disease onset and progression. In this study, we investigated circRNAs implicated in ALS and related motor neuron diseases (MNDs). First, we conducted a systematic review to identify ALS-associated circRNAs, followed by in silico analyses of 15 selected candidates. Our results revealed that hsa_circ_0000099, hsa_circ_0001017, hsa_circ_004846, and hsa_circ_0034880 regulate a high number of ALS-related genes through miRNA sponging. Pathway enrichment analysis indicated that hsa_circ_0000099 is particularly involved in unfolded protein response, oxidative stress, cell cycle regulation, and apoptosis. Protein-RNA interaction analysis further showed that ALS-related circRNAs can sponge 20 RNA-binding proteins, with FMR1, ELAVL1, EIF4A3, and SRSF1 exhibiting the highest number of interactions. Additionally, molecular docking analysis demonstrated that FUS mutations significantly alter its binding affinity to hsa_circ_0000567 and hsa_circ_0060762. RNA-seq data from ALS patients confirmed significant alterations in the expression of host genes of ALS-related circRNAs and hub proteins across affected tissues, including the spinal cord and multiple brain regions. Collectively, these findings support circRNAs as active contributors to ALS pathogenesis. In particular, the host gene of hsa_circ_0000099, which is expressed in the spinal cord and hippocampus, emerges as a potential biomarker for tissue-specific impairment in ALS. Moreover, its regulatory role in key ALS-related cellular pathways underscores its promise as a candidate for biomarker development and therapeutic targeting. Further experimental validation is warranted to confirm its role in ALS pathology. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/677871v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@15d0389org.highwire.dtl.DTLVardef@1934327org.highwire.dtl.DTLVardef@11ddd3aorg.highwire.dtl.DTLVardef@1a74c09_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

Age and dose-dependent effects of alpha-lipoic acid on human microtubule-associated protein tau-induced endoplasmic reticulum unfolded protein response: implications for Alzheimers disease

BackgroundIn human tauopathies, pathological aggregation of misfolded/unfolded proteins particularly microtubule-associated protein tau (MAPT, tau) is considered to be essential mechanisms that trigger the induction of endoplasmic reticulum (ER) stress. Here we assessed the molecular effects of natural antioxidant alpha-lipoic acid (ALA) in human tauR406W (htau)-induced ER unfolded protein response (ERUPR) in the young and older flies. MethodsIn order to reduce htau neurotoxicity during brain development, we used a transgenic model of tauopathy where the maximum toxicity was observed in adult flies. Then, the effects of ALA (0.001, 0.005, and 0.025% w/w of diet) in htau-induced ERUPR in the ages 20 and 30 days were evaluated. ResultsData from expression (mRNA and protein) patterns of htau, analysis of eyes external morphology as well as larvae olfactory memory were confirmed our tauopathy model. Moreover, expression of ERUPR-related proteins involving activating transcription factor 6 (ATF6), inositol regulating enzyme 1 (IRE1), and protein kinase RNA-like ER kinase (PERK) were upregulated and locomotor function decreased in both ages of the model flies. Remarkably, the lower dose of ALA modified ERUPR and supported the reduction of behavioral deficits in youngest adults through enhancement of GRP87/Bip, reduction of ATF6, downregulation of PERK-ATF4 pathway, and activation of the IRE1-XBP1 pathway. On the other hand, only a higher dose of ALA was able to affect the ERUPR via moderation of PERK-ATF4 signaling in the oldest adults. As ALA exerts their higher protective effects on the locomotor function of younger adults when htauR406W expressed in all neurons (htau-elav) and mushroom body neurons (htau-ok), we proposed that ALA has age-dependent effects in this model. ConclusionTaken together, based on our results we conclude that aging potentially influences the ALA effective dose and mechanism of action on tau-induced ERUPR. Further molecular studies will warrant possible therapeutic applications of ALA in age-related tauopathies.

neuroscience↗