Target enzymes in oxaliplatin-induced peripheral neuropathy in Swiss mice: A new acetylcholinesterase inhibitor as therapeutic strategy

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of typical chemotherapeutics among cancer survivors. Despite the recent progress, the effective prevention and treatment strategies for CIPN remain limited. Better understanding of the pathogenesis of CIPN may provide new niches for developing a new ideal therapeutic strategy. This review summarizes the current understanding of CIPN and current recommendations along with completed/active clinical trials and aims to foster translational research to improve the development of effective strategies for managing CIPN.

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Pharmacological augmentation of nicotinamide phosphoribosyltransferase (NAMPT) protects against paclitaxel-induced peripheral neuropathy

eLife ◽

10.7554/elife.29626 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 13

Author(s):

Peter M LoCoco ◽

April L Risinger ◽

Hudson R Smith ◽

Teresa S Chavera ◽

Kelly A Berg ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Anticancer Drug ◽

Therapeutic Strategy ◽

Maximum Tolerated Dose ◽

Cancer Prognosis ◽

Collateral Damage ◽

Peripheral Neurotoxicity ◽

Drug Induced ◽

Nicotinamide Phosphoribosyltransferase ◽

Stimulation Of

Chemotherapy-induced peripheral neuropathy (CIPN) arises from collateral damage to peripheral afferent sensory neurons by anticancer pharmacotherapy, leading to debilitating neuropathic pain. No effective treatment for CIPN exists, short of dose-reduction which worsens cancer prognosis. Here, we report that stimulation of nicotinamide phosphoribosyltransferase (NAMPT) produced robust neuroprotection in an aggressive CIPN model utilizing the frontline anticancer drug, paclitaxel (PTX). Daily treatment of rats with the first-in-class NAMPT stimulator, P7C3-A20, prevented behavioral and histologic indicators of peripheral neuropathy, stimulated tissue NAD recovery, improved general health, and abolished attrition produced by a near maximum-tolerated dose of PTX. Inhibition of NAMPT blocked P7C3-A20-mediated neuroprotection, whereas supplementation with the NAMPT substrate, nicotinamide, potentiated a subthreshold dose of P7C3-A20 to full efficacy. Importantly, P7C3-A20 blocked PTX-induced allodynia in tumored mice without reducing antitumoral efficacy. These findings identify enhancement of NAMPT activity as a promising new therapeutic strategy to protect against anticancer drug-induced peripheral neurotoxicity.

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Regulatory Effects of Astragaloside IV on Hyperglycemia-Induced Mitophagy in Schwann Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2022/7864308 ◽

2022 ◽

Vol 2022 ◽

pp. 1-8

Author(s):

Xiaoyi Wei ◽

Yalin Zheng ◽

Yanke Ai ◽

Buman Li

Keyword(s):

Oxidative Stress ◽

Peripheral Neuropathy ◽

Schwann Cells ◽

Diabetic Peripheral Neuropathy ◽

Therapeutic Strategy ◽

Mitochondrial Morphology ◽

Astragaloside Iv ◽

High Glucose Medium ◽

Regulatory Effects ◽

Related Proteins

Objective. This study aimed to observe the regulatory effects of astragaloside IV (AS-IV) on hyperglycemia-induced mitochondrial damage and mitophagy in Schwann cells and to provide references for clinical trials on AS-IV in the treatment of diabetic peripheral neuropathy. Methods. Schwann cells were grown in a high-glucose medium to construct an autophagy model; the cells were then treated with AS-IV and N-acetylcysteine (control) to observe the regulatory effects of AS-IV on oxidative stress and mitophagy. Results. AS-IV exhibited antioxidant activity and inhibited the overactivation of autophagy in Schwann cells, significantly reducing the level of reactive oxygen species and downregulating the expression of autophagy-related proteins (LC3, PINK, and Parkin) under hyperglycemic conditions, thereby exerting a protective effect on mitochondrial morphology and membrane potential. Conclusion. AS-IV can maintain the mitochondrial function of Schwann cells under hyperglycemic conditions by effectively alleviating oxidative stress and overactivation of mitophagy. The evidence from this study supports an AS-IV-based therapeutic strategy against diabetic peripheral neuropathy.

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Targeting lysosomal cysteine protease cathepsin S reveals immunomodulatory therapeutic strategy for oxaliplatin-induced peripheral neuropathy

Theranostics ◽

10.7150/thno.54793 ◽

2021 ◽

Vol 11 (10) ◽

pp. 4672-4687

Author(s):

Szu-Jung Chen ◽

Li-Hsien Chen ◽

Yu-Min Yeh ◽

Chou-Ching K Lin ◽

Peng-Chan Lin ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Cysteine Protease ◽

Therapeutic Strategy ◽

Cathepsin S ◽

Lysosomal Cysteine Protease

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Alteration of Mitochondria in Oxythiamine-Induced, Acute Thiamine Deficiency in the Mouse

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100091408 ◽

1976 ◽

Vol 34 ◽

pp. 284-285

Author(s):

Itaru Watanabe ◽

Dante G. Scarpelli

Keyword(s):

Electron Microscopy ◽

Adult Male ◽

Thiamine Deficiency ◽

Light And Electron Microscopy ◽

Fatty Change ◽

Deficient Diet ◽

Subcutaneous Injections ◽

Swiss Mice ◽

Time Period ◽

Ad Libitum

Acute thiamine deficiency was produced in mice by the administration of oxythiamine, a thiamine analogue, superimposed upon a thiamine deficient diet. Adult male Swiss mice (30 gm. B.W.) were fed with a thiamine deficient diet ad libitumand were injected with oxythiamine (170 mg/Kg B.W.) subcutaneously on days 4 and 10. On day 11, severe lassitude and anorexia developed, followed by death within 48 hours. The animals treated daily with subcutaneous injections of thiamine (300 μg/Kg B.W.) from day 11 through 15 were kept alive. Similarly, feeding with a diet containing thiamine (600 μg/Kg B.W./day) from day 9 through 17 reversed the condition. During this time period, no fatal illness occurred in the controls which were pair-fed with a thiamine deficient diet.The oxythiamine-treated mice showed a significant enlargement of the liver, which weighed approximately 1.5 times as much as that of the pair-fed controls. By light and electron microscopy, the hepatocytes were markedly swollen due to severe fatty change and swelling of the mitochondria.

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