SUMMARY:
This study demonstrates its effectiveness towards ameliorating biomolecular abnormalities in an in vitro model of CMT1A, an inherited peripheral neuropathy. These findings will facilitate the clinical translation of an electroceutical treatment for CMT1A.
TITLE:
Electroceutical approach ameliorates intracellular PMP22 aggregation and promotes pro-myelinating pathways in a CMT1A in vitro model
DESCRIPTION:
Charcot-Marie-Tooth disease subtype 1A (CMT1A) is one of the most prevalent demyelinating peripheral neuropathies worldwide, caused by duplication of the peripheral myelin protein 22 (PMP22) gene, which is expressed primarily in Schwann cells (SCs). PMP22 overexpression in SCs leads to intracellular aggregation of the protein, which eventually results in demyelination. Unfortunately, previous biochemical approaches have not resulted in an approved treatment for CMT1A disease, compelling the…
CONTENT:
Biosens Bioelectron. 2022 Dec 30;224:115055. doi: 10.1016/j.bios.2022.115055. Online ahead of print.
ABSTRACT
Charcot-Marie-Tooth disease subtype 1A (CMT1A) is one of the most prevalent demyelinating peripheral neuropathies worldwide, caused by duplication of the peripheral myelin protein 22 (PMP22) gene, which is expressed primarily in Schwann cells (SCs). PMP22 overexpression in SCs leads to intracellular aggregation of the protein, which eventually results in demyelination. Unfortunately, previous biochemical approaches have not resulted in an approved treatment for CMT1A disease, compelling the pursuit for a biophysical approach such as electrical stimulation (ES). However, the effects of ES on CMT1A SCs have remained unexplored. In this study, we established PMP22-overexpressed Schwannoma cells as a CMT1A in vitro model, and investigated the biomolecular changes upon applying ES via a custom-made high-throughput ES platform, screening for the condition that delivers optimal therapeutic effects. While PMP22-overexpressed Schwannoma exhibited intracellular PMP22 aggregation, ES at 20 Hz for 1 h improved this phenomenon, bringing PMP22 distribution closer to healthy condition. ES at this condition also enhanced the expression of the genes encoding myelin basic protein (MBP) and myelin-associated glycoprotein (MAG), which are essential for assembling myelin sheath. Furthermore, ES altered the gene expression for myelination-regulating transcription factors Krox-20, Oct-6, c-Jun and Sox10, inducing pro-myelinating effects in PMP22-overexpressed Schwannoma. While electroceuticals has previously been applied in the peripheral nervous system towards acquired peripheral neuropathies such as pain and nerve injury, this study demonstrates its effectiveness towards ameliorating biomolecular abnormalities in an in vitro model of CMT1A, an inherited peripheral neuropathy. These findings will facilitate the clinical translation of an electroceutical treatment for CMT1A.
PMID:36630746 | DOI:10.1016/j.bios.2022.115055
SOURCE:
Biosensors & bioelectronics
TAGS:
#CMT1A
CATEGORY:
Research
SUBCATEGORY:
n/a
DATE – PUBLISHED:
2022-12-31T00:40:31Z
DATE – DOI: 2022-12-31T00:40:31Z
DATE – PUBMED: 2022 Dec 30
DATE OUTPUT MATCHED: True
DATE – ADDED:
Wed, 11 Jan 2023 06:00:00 -0500
DATE – RETRIEVED:
01/12/23 01:03AM
2023-01-12T01:03:06-05:00
FEATURED IMAGE:
Media Uploaded (image/png)
IDENTIFIER:
pmid:36630746,doi:10.1016/j.bios.2022.115055
PUBMED ID:
pubmed:36630746
DOI:
10.1016/j.bios.2022.115055
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36630746/
LINK – DOI:
https://doi.org/10.1016/j.bios.2022.115055
LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0956566322010958
REFERENCES:
CMT Treatment Report, Urgent Research, 2023-01-12T01:03:06-05:00, https://www.cmttreatmentreport.com.