Autophagy-NAD Axis as a Target for Therapeutic Interventions in NPC1 Disease
01 Jan

Autophagy-NAD Axis as a Target for Therapeutic Interventions in NPC1 Disease

Introduction

Targeting the autophagy-NAD axis has been reported be a viable therapeutic strategy for Niemann-Pick type C1 (NPC1) disease. The study suggests that both pharmacological rescue of autophagy deficiency and supplementation of NAD precursors can restore NAD+ level, improve the viability of fibroblasts in NPC1 patients, and induce pluripotent stem cell (iPSC)-derived cortical neurons.

About NPC1 disease 

Niemann-Pick disease, a hereditary chronic neurologic disorder, is categorized into three types, with NPC1 occurring in more different populations. NPC1 disease, an autosomal recessive disorder, is characterized by an enlarged spleen, neurological dysfunctions, and the accumulation of lipids such as sphingolipids and cholesterol. The disease is most commonly caused by mutations in the NPC1 gene which encodes a cholesterol transporter on the lysosomal membrane.

Targeting the autophagy-NAD axis: a promising approach for NPC1 disease

The loss of NPC1 function leads to impaired autophagy/mitophagy, resulting in NAD+ depletion, mitochondrial depolarisation, and apoptotic cell death. However, the use of autophagy inducers (celecoxib or memantine)
and NAD precursors has shown promise in ameliorating the phenotypes observed in mouse and human NPC1 model cells.



Notably, NAD precursor supplementation acts downstream of autophagy dysfunction. Specifically, this supplementation promotes the viability of Npc1-/- MEFs and restores the apoptotic cell death in Npc1-/- cells, but exhibits no or mild upregulation of autophagy function in mouse embryonic fibroblasts (MEFs) and primary fibroblasts. However, autophagy activators not only rescue NAD depletion and cell death in Npc1-/- MEFs, but also restore autophagic flux and mitophagy deficit.



Targeting the autophagy-NAD axis can promote the survival of NPC1 patient-derived primary fibroblasts and protect against cell death of NPC1 patient iPSC-derived cortical neurons. Strikingly, boosting NAD+ level is believed to improve mitochondrial function and ATP generation, potentially replenishing lysosomal degradation capacity and restoring autophagic function in NPC1-mutant neurons.


                                NPC1 patient-derived primary fibroblasts


                             NPC1 patient iPSC-derived cortical neurons


Conclusion

Both autophagy inducers and NAD precursors are effective in ameliorating NPC1 disease, and combining the two may complement their strengths and maximize their effectiveness, opening new insights into the neurodegenerative conditions associated with autophagy and NAD+ defects.

Reference

Kataura T, Sedlackova L, Sun C, et al. Targeting the autophagy-NAD axis protects against cell death in Niemann-Pick type C1 disease models. Cell Death Dis. 2024;15(5):382. Published 2024 May 31. doi:10.1038/s41419-024-06770-y

BONTAC NAD

BONTAC has been dedicated to the R&D, manufacture and sale of raw materials for coenzyme and natural products since 2012, with self-owned factories, over 170 global patents as well as strong R&D team. BONTAC has rich R&D experience and advanced technology in the biosynthesis of NAD and its precursors (eg. NMN and NR). There are various types of NAD to be selected, encompassing NAD ER Grade (endoxin removal), NAD Grade I (IVD/dietary supplement/cosmetics raw powder), NAD Grade II (API/intermediates) and NAD Grade IV (if any higher requirement on the solubility), which can be provided in the form of lyophilized powder or crystalline powder. The purity of BONTAC NAD can reach above 98%.

Disclaimer

This article is based on the reference in the academic journal. The relevant information is provided for sharing and learning purposes only, and does not represent any medical advice purposes. If there is any infringement, please contact the author for deletion. The views expressed in this article do not represent the position of BONTAC. Under no circumstances will BONTAC be responsible in any way for any claims, damages, losses, expenses or costs arising directly or indirectly from your reliance on the information and material on this website.

Tags: nmn powder nad powder nadh powder nmnh powder nmn manufacturer nad manufacturer nadh manufacturer nmnh manufacturer nmn supplement

best nad powder coenzyme best nad powder factory best nad powder manufacturer best nad powder supplement best nad powder supplier buy nad powder coenzyme buy nad powder factory buy nad powder manufacturer buy nad powder supplement buy nad powder supplier high purity nad powder coenzyme high purity nad powder factory high purity nad powder manufacturer high purity nad powder supplement high purity nad powder supplier high quality nad powder coenzyme high quality nad powder factory high quality nad powder manufacturer high quality nad powder supplement high quality nad powder supplier purchase nad powder coenzyme purchase nad powder factory purchase nad powder manufacturer purchase nad powder supplement purchase nad powder supplier
best nadh powder coenzyme best nadh powder factory best nadh powder manufacturer best nadh powder supplement best nadh powder supplier buy nadh powder coenzyme buy nadh powder factory buy nadh powder manufacturer buy nadh powder supplement buy nadh powder supplier high purity nadh powder coenzyme high purity nadh powder factory high purity nadh powder manufacturer high purity nadh powder supplement high purity nadh powder supplier high quality nadh powder coenzyme high quality nadh powder factory high quality nadh powder manufacturer high quality nadh powder supplement high quality nadh powder supplier purchase nadh powder coenzyme purchase nadh powder factory purchase nadh powder manufacturer purchase nadh powder supplement purchase nadh powder supplier
best nmnh powder coenzyme best nmnh powder factory best nmnh powder manufacturer best nmnh powder supplement best nmnh powder supplier buy nmnh powder buy nmnh powder coenzyme buy nmnh powder factory buy nmnh powder manufacturer buy nmnh powder supplement buy nmnh powder supplier high purity nmnh powder coenzyme high purity nmnh powder factory high purity nmnh powder manufacturer high purity nmnh powder supplement high purity nmnh powder supplier high quality nmnh powder high quality nmnh powder coenzyme high quality nmnh powder factory high quality nmnh powder manufacturer high quality nmnh powder supplement high quality nmnh powder supplier hot sale nmnh powder longevity nmnh powder coenzyme longevity nmnh powder factory longevity nmnh powder manufacturer longevity nmnh powder supplement longevity nmnh powder supplier nmnh powder company nmnh powder manufacturer
purchase nmn manufacturer supplier high quality nmn manufacturer supplement purchase nmn manufacturer factory purchase nmn manufacturer coenzyme longevity nmn manufacturer supplier longevity nmn manufacturer production high quality nmn manufacturer factory purchase nmn manufacturer production high purity nmn manufacturer supplement purchase nmn manufacturer supplement high purity nmn manufacturer factory high purity nmn manufacturer production best nmn manufacturer coenzyme best nmn manufacturer supplement best nmn manufacturer supplier buy nmn manufacturer coenzyme buy nmn manufacturer supplement buy nmn manufacturer production best nmn manufacturer production high purity nmn manufacturer coenzyme high quality nmn manufacturer supplier high purity nmn manufacturer supplier longevity nmn manufacturer factory longevity nmn manufacturer coenzyme longevity nmn manufacturer supplement high quality nmn manufacturer production high quality nmn manufacturer coenzyme buy nmn manufacturer factory buy nmn manufacturer supplier best nmn manufacturer factory
best nad manufacturer best nad manufacturer coenzyme best nad manufacturer factory best nad manufacturer supplement best nad manufacturer supplier buy nad manufacturer coenzyme buy nad manufacturer factory buy nad manufacturer production buy nad manufacturer supplement buy nad manufacturer supplier high purity nad manufacturer coenzyme high purity nad manufacturer factory high purity nad manufacturer production high purity nad manufacturer supplement high purity nad manufacturer supplier high quality nad manufacturer coenzyme high quality nad manufacturer factory high quality nad manufacturer production high quality nad manufacturer supplement high quality nad manufacturer supplier best nad manufacturer production
best nadh manufacturer best nadh manufacturer coenzyme best nadh manufacturer factory best nadh manufacturer supplement best nadh manufacturer supplier buy nadh manufacturer coenzyme buy nadh manufacturer factory buy nadh manufacturer production buy nadh manufacturer supplement buy nadh manufacturer supplier high purity nadh manufacturer coenzyme high purity nadh manufacturer factory high purity nadh manufacturer production high purity nadh manufacturer supplement high purity nadh manufacturer supplier high quality nadh manufacturer coenzyme high quality nadh manufacturer factory high quality nadh manufacturer production high quality nadh manufacturer supplement high quality nadh manufacturer supplier purchase nadh manufacturer coenzyme purchase nadh manufacturer factory purchase nadh manufacturer production purchase nadh manufacturer supplement purchase nadh manufacturer supplier best nadh manufacturer production
high quality nmnh manufacturer coenzyme longevity nmnh manufacturer coenzyme purchase nmnh manufacturer supplier longevity nmnh manufacturer supplement high quality nmnh manufacturer production longevity nmnh manufacturer factory high purity nmnh manufacturer factory high purity nmnh manufacturer coenzyme high quality nmnh manufacturer supplement high purity nmnh manufacturer supplement purchase nmnh manufacturer factory high purity nmnh manufacturer production best nmnh manufacturer factory best nmnh manufacturer coenzyme longevity nmnh manufacturer production high quality nmnh manufacturer factory buy nmnh manufacturer supplier purchase nmnh manufacturer production purchase nmnh manufacturer coenzyme buy nmnh manufacturer supplement best nmnh manufacturer production high purity nmnh manufacturer supplier high quality nmnh manufacturer supplier buy nmnh manufacturer factory buy nmnh manufacturer coenzyme best nmnh manufacturer supplement best nmnh manufacturer supplier longevity nmnh manufacturer supplier purchase nmnh manufacturer supplement buy nmnh manufacturer production
what is nmn supplement top selling nmn supplement top quality nmn supplement nmn supplement supplier nmn supplement production nmn supplement price nmn supplement manufacturer nmn supplement in china nmn supplement for sale nmn supplement factory nmn supplement david sinclair nmn supplement company hot sale nmn supplement high quality nmn supplement china nmn supplement buy nmn supplement best price nmn supplement best nmn supplement david sinclair best nmn supplement