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Mitigation of pathological parameters under Jagged1 influence in DMD knockout zebrafish and patient-derived myoblast cultures

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Title Mitigation of pathological parameters under Jagged1 influence in DMD knockout zebrafish and patient-derived myoblast cultures
 
Creator Nesari, Vishakha
Vaishnav, Juhi
Sharma, Shashikant
Nongthomba, Upendra
Balakrishnan, Suresh
 
Subject Duchenne Muscular Dystrophy
Golden retriever muscular dystrophy (GRMD) model
Jagged1 peptide
Myotubes
Zebrafish
 
Description 681-689
Duchenne muscular dystrophy (DMD) is an X-linked, degenerative disease mainly affecting male children, with
progressive weakness of whole-body skeletal muscles and the heart. There is a gradual loss of ambulation, heart weakness,
and breathing capacity by late teens. Heart or lung dysfunction causes early death in patients during the second or third
decade. Steroid treatment delays disease progression by 2-3 years, albeit with serious side effects. The few FDA-approved
gene therapies are mutation-specific and exorbitantly priced. There is an unmet medical need for the children affected with
DMD. Interestingly, a previous study showed that single nucleotide change caused Jagged1 overexpression, which resulted
in avoidance of early death and ambulatory loss in 1-1.5-year-old golden retriever dogs severely affected with muscular
dystrophy. Identifying the pathological processes mitigated by Jagged1 overexpression might help understand the
mechanism of this rescue. Hence, we generated DMD knockout in zebrafish, another severe model of DMD with
overexpression of the human Jagged1 (JAG1). Pathological aspects like cell death, cell proliferation, cytoplasmic and
mitochondrial oxidative stress were compared between dystrophic, rescued, and control groups. Surprisingly, JAG1
increased mitochondrial oxidative stress during rescue, while reducing other pathological processes. Similarly, increased
mitochondrial ROS production occurred with Jag1 peptide treatment in in vitro differentiated patient-derived myotubes,
suggesting a conserved mechanism involved in the rescue.
 
Date 2023-09-20T05:18:23Z
2023-09-20T05:18:23Z
2023-09
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://nopr.niscpr.res.in/handle/123456789/62534
https://doi.org/10.56042/ijbb.v60i9.3895
 
Language en
 
Publisher NIScPR-CSIR,India
 
Source IJBB Vol.60(09) [September 2023]