Work

RNA helicase maheshvara interacts with TDP-43 and exacerbates neurodegeneration in Drosophila model of amyotrophic lateral sclerosis

Year: 2025

Type: article

Abstract: Drosophila maheshvara (mahe) encodes a conserved DEAD box RNA helicase that regulates various important signaling pathways like Notch and JAK/STAT, pathways that have been functionally implicated in neuronal development. In order to identify novel modulators of mahe as well as to unravel its role in neurodegenerative disorders, a genetic modifier screen using Drosophila models of neurodegenerative disorders was carried out. From this screen, we identified mahe to be a potent modifier of TDP-43 mediated proteinopathy in Drosophila model of Amyotrophic Lateral Sclerosis (ALS). We demonstrate that Mahe genetically interacts and associates with cytosolic hyperphosphorylated toxic aggregates of TDP-43 leading to enhanced TDP-43 mediated neurodegenerative phenotype. Increased autophagy, cytoskeletal disruption, and FMRP-mediated translational repression of neuronal target Futsch were observed, potentially contributing to neuronal dysfunction. The current study indicates a strong interaction of mahe and TDP-43 (TARDBP) resulting in augmentation of TDP-43 mediated neurodegenerative phenotypes which parallels ALS clinical pathology.

Source: Neurobiology of Disease

DOI: 10.1016/j.nbd.2025.107036

Authors: Pranjali Pandey, Rituparna Das, Harshita Yadav, Ashim Mukherjee, Mousumi Mutsuddi

Institutions: Banaras Hindu University, University of Manchester

Language: English

Topic: Amyotrophic Lateral Sclerosis Research

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,180