---
title: "Dysregulation of the SARA–Smurf2 Axis in Temporal Lobe Epilepsy and Modulation by Losartan"
id: "biorxiv-10-dysregulation-of-the-sara-smurf2-regulatory-axis-in-temporal-lobe-epilepsy"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-10-dysregulation-of-the-sara-smurf2-regulatory-axis-in-temporal-lobe-epilepsy"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.08.10.743913v1?rss=1"
published_at: "2026-08-17T10:57:14.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Dysregulation of the SARA–Smurf2 Axis in Temporal Lobe Epilepsy and Modulation by Losartan
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-10-dysregulation-of-the-sara-smurf2-regulatory-axis-in-temporal-lobe-epilepsy
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.08.10.743913v1?rss=1)
- **Published At:** 2026-08-17T10:57:14.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Temporal lobe epilepsy (TLE) is linked to dysregulated **TGFβ** signaling, a pathway implicated in epileptogenesis. SARA (Smad Anchor for Receptor Activation) is a central regulator of TGFβ signaling and is targeted for ubiquitination by the E3 ligase **Smurf2**. - The study examined the SARA–Smurf2 regulatory axis in a pilocarpine-induced status epilepticus (SE) rat model and in astrocytes derived from patients with refractory TLE to determine whether this axis is altered in TLE and whether it is modifiable by pharmacologic intervention. - In the SE rat model, **SARA** and **GFAP** levels were significantly increased, suggesting reactive astrocytosis and SARA accumulation. Induction of **Smurf2** in SE animals was present but judged insufficient to prevent SARA accumulation. - In astrocytes obtained from patients with refractory TLE, researchers observed increased **SARA** and **GFAP** immunoreactivity, combined with reduced **Smurf2** immunoreactivity and altered Smurf2 subcellular localization. - Treatment with **Losartan** in both experimental systems restored SARA and Smurf2 immunoreactivity toward patterns seen in controls and, in SE animals, reduced seizure frequency and duration. - The authors propose that dysregulation of the **SARA–Smurf2** axis is a molecular signature of TLE, identify **SARA** as a potential therapeutic target, and present preclinical evidence supporting repositioning **Losartan** as a candidate treatment for drug-resistant epilepsy, while noting that further translational and clinical work is required. - The preprint reports no competing interests and lists national and international research funders. Specific numerical data, statistical values, and detailed experimental parameters were not reported in the source summary and therefore are not provided here.
## Clinical Analysis & Structured Key Points
Dysregulation of the SARA-Smurf2 Regulatory Axis in Temporal Lobe Epilepsy | bioRxiv Skip to main content New Results Dysregulation of the SARA-Smurf2 Regulatory Axis in Temporal Lobe Epilepsy Estefania Clavenzani , Juan Manuel Bourbotte Asensio , Laura Ester Montroull , Jesica Piovano , Soledad De Olmos , Marisa Gigena , Sebastian Manuel Bairo , Mariana Bollo , Ariel Martinez , Juan Carlos De Battista , Marco Lisicki , Cecilia Conde doi: https://doi.org/10.64898/2026.08.10.743913 Estefania Clavenzani 1 Instituto de Investigacion Medica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de Cordoba; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Juan Manuel Bourbotte Asensio 1 Instituto de Investigacion Medica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de Cordoba; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Laura Ester Montroull 1 Instituto de Investigacion Medica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de Cordoba; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jesica Piovano 1 Instituto de Investigacion Medica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de Cordoba; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Soledad De Olmos 1 Instituto de Investigacion Medica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de Cordoba; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marisa Gigena 1 Instituto de Investigacion Medica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de Cordoba; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sebastian Manuel Bairo 1 Instituto de Investigacion Medica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de Cordoba; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mariana Bollo 1 Instituto de Investigacion Medica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de Cordoba; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ariel Martinez 2 Hospital de Niňos de la Santisima Trinidad de Cordoba, Argentina; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Juan Carlos De Battista 3 Hospital Privado Universitario de Cordoba, Argentina Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marco Lisicki 1 Instituto de Investigacion Medica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de Cordoba; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Cecilia Conde 1 Instituto de Investigacion Medica M y M Ferreyra, INIMEC-CONICET, Universidad Nacional de Cordoba; Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: cconde{at}immf.uncor.edu Abstract Info/History Metrics Preview PDF Abstract Temporal lobe epilepsy (TLE) is associated with dysregulation of transforming growth factor β ; (TGFβ) signaling, a key contributor to epileptogenesis. SARA (Smad Anchor for Receptor Activation), a central regulator of this pathway, is controlled by the E3 ubiquitin ligase Smurf2 through ubiquitination. However, the role of the SARA—Smurf2 axis in regulating TGFβ signaling during TLE has not previously been described, and whether this pathway can be therapeutically targeted remains unknown. Using a pilocarpine-induced status epilepticus (SE) model and astrocytes derived from patients with refractory TLE, we identified dysregulation of the SARA—Smurf2 pathway in both experimental systems. In SE rats, SARA and Glial Fibrillary Acidic Protein (GFAP) levels were significantly increased, whereas Smurf2 induction was insufficient to prevent SARA accumulation. In TLE-derived astrocytes, increased SARA and GFAP immunoreactivity was accompanied by reduced Smurf2 immunoreactivity and altered Smurf2 subcellular distribution. Losartan treatment restored SARA and Smurf2 immunoreactivity toward a control-like pattern in both models and reduced seizure frequency and duration in SE animals. These findings point towards a dysregulation of the SARA—Smurf2 axis as a molecular signature of TLE, support SARA as a potential therapeutic target, and provide experimental evidence for the repositioning of Losartan as a potential treatment alternative for drug-resistant epilepsy, warranting further translational and clinical investigation. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación, https://ror.org/03stxzb56 , PICT2020-01268 International Brain Research Organization , Collaborative Research Grant 2023 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Back to top Previous Next Posted August 17, 2026. Download PDF Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Dysregulation of the SARA-Smurf2 Regulatory Axis in Temporal Lobe Epilepsy Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. 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