Promotion of degradative autophagy by 6 ‐bromoindirubin‐3′‐oxime attenuates neuropathy

Tunicamycin increases peripheral neuropathy subsequently treatment with 6-BIO reduces peripheral neuropathy and increases degradative autophagy and reduces secretory autophagy. AbstractDamage 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 (C TSD), 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 lys...

Source: BioFactors - May 31, 2023 Category: Biochemistry Authors: Praveen Jaiswar, Mitali Bhate, Avadhesha Surolia Tags: RESEARCH ARTICLE Source Type: research