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Promotion of degradative autophagy by 6-bromoindirubin-3�-oxime attenuates neuropathy

Jaiswar, P and Bhate, M and Surolia, A (2023) Promotion of degradative autophagy by 6-bromoindirubin-3�-oxime attenuates neuropathy. In: BioFactors .

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Official URL: https://doi.org/10.1002/biof.1977


Damage to the central or peripheral nervous system causes neuropathic pain. Endoplasmic reticulum (ER) stress plays a role in peripheral neuropathy. Increase in ER stress is seen in diabetic neuropathy. Inducers of ER stress also give rise to peripheral neuropathy. ER stress leads to the formation of autophagosome but as their degradation is also stalled during ER stress accumulation of autophagosomes is seen. Accumulation of autophagosomes has deleterious effects on cells. In the present study, we show that treatment with tunicamycin (TM) (ER stress inducer) in mice leads to peripheral neuropathy as assessed by Von Frey and Hot plate method. Administration of a promoter of autophagy viz. 6-bromoindirubin-3′-oxime (6-BIO) subsequent to ER stress induced by TM exhibits a decrease in peripheral neuropathy. 6-BIO was also effective in reducing diabetic peripheral neuropathy. To understand the type of autophagy activated, SH-SY5Y cells were treated with 6-BIO after TM treatment. Levels of cathepsin D (CTSD), a marker for degradative autophagy was higher in cells treated with 6-BIO after TM treatment compared to only TM-treated SH-SY5Y cells while levels of Rab8A,—a marker for secretory autophagy was reduced. Furthermore, in parallel during ER stress secretory, we noted increased levels of lysozyme in autophagosomes destined for secretion. Cells treated with 6-BIO showed reduction of lysozyme in secretory autophagosomes. This shows that 6-BIO increased degradative autophagy and reduced the secretory autophagy. 6-BIO also reduced the caspase-3 activity in 6-BIO-treated cells. Thus, 6-BIO reduced neuropathy in animals by activating degradative autophagy and reducing the secretory autophagy.

Item Type: Journal Article
Publication: BioFactors
Publisher: John Wiley and Sons Inc
Additional Information: The copyright for this article belongs to the John Wiley and Sons Inc.
Keywords: 6-BIO; autophagy; diabetic neuropathy; ER stress; neuropathy
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 13 Jul 2023 09:46
Last Modified: 13 Jul 2023 09:46
URI: https://eprints.iisc.ac.in/id/eprint/82406

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