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MG132 Induces Progerin Clearance and Improves Disease Phenotypes in HGPS-like Patients’ Cells
- Source :
- Cells, Vol 11, Iss 4, p 610 (2022)
- Publication Year :
- 2022
- Publisher :
- MDPI AG, 2022.
-
Abstract
- Progeroid syndromes (PS), including Hutchinson-Gilford Progeria Syndrome (HGPS), are premature and accelerated aging diseases, characterized by clinical features mimicking physiological aging. Most classical HGPS patients carry a de novo point mutation within exon 11 of the LMNA gene encoding A-type lamins. This mutation activates a cryptic splice site, leading to the production of a truncated prelamin A, called prelamin A ∆50 or progerin, that accumulates in HGPS cell nuclei and is a hallmark of the disease. Some patients with PS carry other LMNA mutations and are named “HGPS-like” patients. They produce progerin and/or other truncated prelamin A isoforms (∆35 and ∆90). We previously found that MG132, a proteasome inhibitor, induced progerin clearance in classical HGPS through autophagy activation and splicing regulation. Here, we show that MG132 induces aberrant prelamin A clearance and improves cellular phenotypes in HGPS-like patients’ cells other than those previously described in classical HGPS. These results provide preclinical proof of principle for the use of a promising class of molecules toward a potential therapy for children with HGPS-like or classical HGPS.
- Subjects :
- progeria-like
MAD-B
progerin
prelamin A Δ90
prelamin A Δ35
MG132
Cytology
QH573-671
Subjects
Details
- Language :
- English
- ISSN :
- 11040610 and 20734409
- Volume :
- 11
- Issue :
- 4
- Database :
- Directory of Open Access Journals
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.5b13b46a4b71430faf1e116cd2bbaac3
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/cells11040610