A novel (-)-(2S)-7,4'-dihydroxyflavanone compound for treating age-related diabetes mellitus through immunoinformatics-guided activation of CISD3.
CDGSH iron-sulfur domain (CISD) proteins
CISD3
Calcium levels
Diabetes mellitus
Endoplasmic reticulum
Redox status
Wolfram syndrome
Journal
Biogerontology
ISSN: 1573-6768
Titre abrégé: Biogerontology
Pays: Netherlands
ID NLM: 100930043
Informations de publication
Date de publication:
29 Oct 2024
29 Oct 2024
Historique:
received:
12
08
2024
accepted:
23
09
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
The iron-sulfur domain (CISD) proteins of CDGSH are classified into three classes: CISD1, CISD2, and CISD3. During premature ageing, mutations that affect these proteins, namely their binding sites, could result in reduced protein production and an inability to preserve cellular integrity. Consequently, this leads to the development of conditions such as diabetes. Notably, CISD3 plays a crucial role in the management of age-related disorders such as Wolfram syndrome, which is often referred to as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Computational analyses have predicted that CISD3 regulates the redox state, safeguards the endoplasmic reticulum and mitochondria, and maintains intracellular calcium levels. CISD3, a member of a recently discovered gene family associated with the CDGSH iron protein apoptotic compensatory response, fulfils a crucial function in mitigating the effects of accelerated ageing. The compound "(-)-(2S)-7,4'-Dihydroxyflavanone" has been discovered by computational drug design as a possible activator of CISD3. It shows potential therapeutic benefits in ameliorating metabolic dysfunction and enhancing glucose regulation. The ligand binds to the binding pocket of the CISD3 protein, increasing the stability of the protein and enhancing its functionality. The current research investigates the binding processes of the molecule in various structures and its anticipated effects on these tissues, therefore providing valuable insights into the mitigation of age-related diabetes and metabolic dysfunction. The projected tripling of the worldwide population of individuals aged 50 and above by 2050 necessitates the urgent development of immunoinformatics-based approaches, including pharmaceutical therapies that target CISD3, to prevent age-related pathologies. The stimulation of CISD3, namely by compounds such as "(-)-(2S)-7,4'-Dihydroxyflavanone", has the potential to counteract telomere shortening and improve metabolic pathways.
Identifiants
pubmed: 39470889
doi: 10.1007/s10522-024-10147-1
pii: 10.1007/s10522-024-10147-1
doi:
Substances chimiques
Flavanones
0
Hypoglycemic Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
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