Elevated constitutive expression of Hsp40 chaperone Sis1 reduces TDP-43 aggregation-induced oxidative stress in Ire1 pathway dependent-manner in yeast TDP-43 proteinopathy model of amyotrophic lateral sclerosis

Bharathi, Vidhya and Bajpai, Akarsh and Patel, Basant Kumar and et al, . (2022) Elevated constitutive expression of Hsp40 chaperone Sis1 reduces TDP-43 aggregation-induced oxidative stress in Ire1 pathway dependent-manner in yeast TDP-43 proteinopathy model of amyotrophic lateral sclerosis. Biochemical and Biophysical Research Communications, 595. pp. 28-34. ISSN 0006-291X

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Abstract

Oxidative stress is a therapeutic target in TDP-43 proteinopathies like amyotrophic lateral sclerosis (ALS) and FTLD-TDP. TDP-43 over-expression causes oxidative stress in yeast model of ALS. Previously, we developed a red/white color conversion reporter assay using ade1 or ade2 mutant yeast to examine oxidative stress induced by expression of amyloidogenic proteins. Also, a previous study showed that overexpression of yeast Hsp40 chaperone Sis1 could mitigate the toxicity and proteosomal blockage induced by TDP-43 over-expression. Here, using the red/white reporter yeast assay and also by CellROX-staining, we found that an elevated expression of Sis1 mitigates the TDP-43-induced oxidative stress. Furthermore, as redox signalling and the ER stress response pathways cross-talk, we checked if the Sis1-mediated mitigation of the TDP-43-induced oxidative stress can also be observed in yeast deleted for ER stress response gene, IRE1. We find that in the yeast deleted for the IRE1 gene, the elevated expression of Sis1 fails to neutralize the TDP-43-induced oxidative stress. Taken together, Hsp40 chaperone modulation can be further examined towards therapeutic research on the TDP-43 proteinopathies. © 2022 Elsevier Inc.

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IITH Creators:

IITH Creators	ORCiD
Patel, Basant Kumar	http://orcid.org/0000-0001-9465-4803

Item Type:

Article

Additional Information:

We thank Prof. Susan W Liebman, UNR, USA, for gifting plasmids and yeast strains. VB thanks DBT, Govt. of India, for senior research fellowship (SRF). AB is thankful to MoE, Govt. of India, for SRF. ITP thanks MoE for research assistantship. Basant K Patel thanks SERB-DST, Govt. of India for research grant- SERB/CRG/2021/006856.

Uncontrolled Keywords:

ALS; Hsp40; Ire1; ROS; Sis1; TDP-43

Subjects:

Others > Biotechnology

Divisions:

Department of Biotechnology

Depositing User:

. LibTrainee 2021

Date Deposited:

22 Jul 2022 06:28

Last Modified:

22 Jul 2022 06:28