Exp Neurobiol.
2024 Dec;33(6):266-281. 10.5607/en24025.
The Multi-targeted Effect of Fascaplysin on the Proliferation and Dedifferentiation of Schwann Cells Inhibits Peripheral Nerve Degeneration by Blocking CDK4/6 and Androgen Receptor
- Affiliations
-
- 1Department of Anesthesiology and Pain Medicine, Kosin University, College of Medicine, Busan 49267, Korea
- 2Department of Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea
- 3Department of Pharmacology, College of Medicine, Kyung Hee University, Seoul 02447, Korea
- 4Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul 02447, Korea
- 5Department of Neurology, Kyung Hee University Hospital, College of Medicine, Kyung Hee University, Seoul 02447, Korea
- 6Department of Pathology, Kyung Hee University Hospital, College of Medicine, Kyung Hee University, Seoul 02447, Korea
- 7Division of Neuroanatomy, Department of Neuroscience,Yamaguchi University, Graduate School of Medicine, Yamaguchi 755-8505, Japan
- 8Department of Digital Health, College of Medicine, Kyung Hee University, Seoul 02447, Korea
- 9Department of Anatomy and Cell Biology, Dong-A University, College of Medicine, Busan 49201, Korea
- KMID: 2564176
- DOI: http://doi.org/10.5607/en24025
Abstract
- Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation. AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Transient lysosomal activation is essential for p75 nerve growth factor receptor expression in myelinated Schwann cells during Wallerian degeneration
- Chiral 1,4-oxazepan-3-one Targeting Schwann Cells Exhibits Morphometrically Inhibitory Effects on Wallerian Degeneration
- Nidogen Plays a Role in the Regenerative Axon Growth of Adult Sensory Neurons Through Schwann Cells
- Mitogen Activated Protein Kinase Family Proteins and c-jun Signaling in Injury-induced Schwann Cell Plasticity
- Double-stranded RNA Induces Inflammatory Gene Expression in Schwann Cells: Implication in the Wallerian Degeneration
