更新于：2024-11-01

beclin-1 x PMP22

更新于：2024-11-01

基本信息

关联

项与 beclin-1 x PMP22 相关的药物

SAM-0022

靶点

PMP22 x beclin-1

作用机制

PMP22抑制剂 [+1]

在研机构

Samsara Therapeutics, Inc.初创企业

原研机构

Samsara Therapeutics, Inc.初创企业

在研适应症

腓骨肌萎缩症Ia型

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 beclin-1 x PMP22 相关的临床结果

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100 项与 beclin-1 x PMP22 相关的转化医学

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0 项与 beclin-1 x PMP22 相关的专利（医药）

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项与 beclin-1 x PMP22 相关的文献（医药）

2019-11-01·Annals of Translational Medicine4区 · 医学

Isoquercitrin promotes peripheral nerve regeneration through inhibiting oxidative stress following sciatic crush injury in mice

4区 · 医学

Article

作者: Zhong, Lou ; Qiu, Jiaying ; Wang, Lingbin ; Zhang, Qiuyu ; Ding, Fei ; Sun, Hualin ; Yang, Xiaoming ; Huang, Ziwei ; Bao, Yuhua ; Ma, Wenjing

BACKGROUNDOxidative stress has been recognized to play a crucial role in the pathogenesis of peripheral nerve injury. Isoquercitrin (quercetin-3-glucoside) is a flavonoid that exhibited many biological activities, including anti-oxidative effect. However, it is unclear whether isoquercitrin has protective effects on peripheral nerve injury.METHODSMice treated by isoquercitrin were used as a case group, and mice injected with saline was the control group. Sciatic behavioral function was assessed using SFI and CMAPs were measured by electrophysiology. Schwann cells proliferation and migration were tested using EdU staining and Transwell migration chambers respectively. The expression of oxidative stress related factors were detected by qRT-PCR and Western blotting.RESULTSIn present study, our results demonstrated that isoquercitrin (20 mg/kg/day) treatment achieved significantly higher SFI and higher amplitude of CMAP, promoted the nerve regeneration and remyelination, increased the production of GAP43, NF200, MAG and PMP22, alleviated target muscle atrophy and autophagy, and suppressed the expression of ATG7, PINK1 and Beclin1 in soleus muscles after sciatic nerve crush. In vitro studies found that isoquercitrin promoted the axonal regeneration of DRGs neurons, the proliferation and migration of Schwann cells, and the expression of proliferating cell nuclear antigen (PCNA) in Schwann cells. The administration of isoquercitrin at 40 and 320 µM showed a dose dependent, and high doses of isoquercitrin (160 and 320 µM) showed better performance in promoting axonal regeneration of DRGs neurons, and the proliferation and migration of Schwann cells than low dose of isoquercitrin (40 µM). Furthermore, isoquercitrin significantly inhibited oxidative stress through reducing the production of Nox4 and Duox1, and promoting the expression of Nrf2 and SOD2 in soleus muscles after sciatic nerve crush.CONCLUSIONSIsoquercitrin may promote motor functional recovery and nerve regeneration following peripheral nerve injury though inhibition of oxidative stress, which highlighted the therapeutic values of isoquercitrin as a neuroprotective drug for peripheral nerve repair applications.

2017-08-01·Biomedicine & Pharmacotherapy2区 · 医学

Curcumin accelerates the repair of sciatic nerve injury in rats through reducing Schwann cells apoptosis and promoting myelinization

2区 · 医学

Article

作者: Li, Xiaoling ; Zhao, Zhiwei ; Li, Qing

BACKGROUNDSchwann cells (SCs) play an indispensable role in the repair and regeneration of injured peripheral nerve. Curcumin can reduce SCs apoptosis, and promote the regeneration and functional recovery of injured peripheral nerves. However, the corresponding mechanisms are not clear.OBJECTIVEThe article was aimed to explore the effect and corresponding mechanisms of curcumin on the repair of sciatic nerve injury in rats.METHODSAfter surgery induced sciatic nerve injury, the model rats were divided into three groups and treated with curcumin, curcumin+PD98059 and curcumin+IGF-1 respectively for 4days. The phosphorylation of Erk1/2 and Akt, and the expression of LC3-II, Beclin 1 and p62 were measured using western blotting. After treatment for 60days, myelination of the injured sciatic nerve was evaluated by MBP immunohistochemical staining and the expression of PMP22, Fibrin and S100 were determined using qRT-PCR and western blotting. In vitro, RSC96 cells were starved for 12h to induce autophagy, and received DMSO, curcumin, PD98059+curcumin, IGF-1+curcumin and BFA1 respectively. The phosphorylation of Erk1/2、Akt and the expression of LC3-II, Beclin 1, p62, PMP22, Fibrin and S100 were measured using western blotting, and the cell apoptosis was detected by flow cytometry.RESULTSCurcumin could promote injury-induced cell autophagy, remyelination and axon regeneration in sciatic nerve of rats. In vitro, curcumin could accelerate cell autophagy through regulating autophagy related Erk1/2 and Akt pathway, prevent cell apoptosis and promote expression of PMP22 and S100, and reduced deposition of Fibrin in cultured RSC96 SCs.CONCLUSIONSCurcumin could accelerate injured sciatic nerve repair in rats through reducing SCs apoptosis and promoting myelinization.