Molecular Insights into the Interaction of Cathepsin D and Iron in Chronic Wound Healing: Exploring Therapeutic Potential and Mechanisms DOI Creative Commons

María Rodríguez-Moreno,

Isabel Legáz

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 544 - 544

Published: Feb. 21, 2025

Background: Chronic wounds, such as diabetic ulcers, often fail to progress through healing due persistent inflammation, infections, and extracellular matrix (ECM) imbalances. Cathepsin D, an aspartate protease active in acidic environments, plays a pivotal role wound by mediating inflammatory responses, ECM remodeling, macrophage phenotype transitions. Its dysregulation, however, can impair healing, highlighting the need for targeted modulation of its activity. The aim this study was investigate molecular interaction between Fe2+ cathepsin D’s catalytic core ionic zipper under physiological conditions identify strategies enhance tissue repair accelerate chronic wounds. Methods: structure D obtained from Protein Data Bank (PDB) analyzed using UCSF Chimera. Molecular interactions ferrous ions (Fe2+) were studied, focusing on key residues (D33 D231) (E5, E180, D187). Results: Our results showed that form 96 kDa dimer, consisted heterodimers with distinct amino acid chains, where D33 D231 formed site, E5, D187 constituted zipper. A functional pocket containing conserved D231, essential proteolytic activity, identified. At pH (~7.5), exhibited most potent Fe2+, energies −7 × 1017 J at oxygen atoms carboxylate group (OD1) α-carbon (CA) atoms, whereas slightly lower −6 γ-carbon atom (CG) CA atoms. (~4), E5 primary interacting residue, shortest distance (2.69 Å), stable across several emphasizing metal binding. Conclusions: strongly influence Fe2. pH, demonstrate robust energetically efficient binding Fe2+. same time, conditions, emerges residue involved, potentially affecting D. These insights provide foundation targeting specific modulate presenting promising opportunities therapeutic aimed improving healing.

Language: Английский

Advancements in autophagy perturbations in Alzheimer’s disease: Molecular aspects and therapeutics DOI

Rishika Dhapola,

Sneha Kumari,

Prajjwal Sharma

et al.

Brain Research, Journal Year: 2025, Volume and Issue: 1851, P. 149494 - 149494

Published: Feb. 6, 2025

Language: Английский

Citations

3
Potential therapeutic targets for Alzheimer’s disease: Fibroblast growth factors and their regulation of ferroptosis, pyroptosis and autophagy DOI
Yiwei Li,

Chenbo Yang,

Xiaonan Liu

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Molecular Insights into the Interaction of Cathepsin D and Iron in Chronic Wound Healing: Exploring Therapeutic Potential and Mechanisms DOI Creative Commons

María Rodríguez-Moreno,

Isabel Legáz

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 544 - 544

Published: Feb. 21, 2025

Background: Chronic wounds, such as diabetic ulcers, often fail to progress through healing due persistent inflammation, infections, and extracellular matrix (ECM) imbalances. Cathepsin D, an aspartate protease active in acidic environments, plays a pivotal role wound by mediating inflammatory responses, ECM remodeling, macrophage phenotype transitions. Its dysregulation, however, can impair healing, highlighting the need for targeted modulation of its activity. The aim this study was investigate molecular interaction between Fe2+ cathepsin D’s catalytic core ionic zipper under physiological conditions identify strategies enhance tissue repair accelerate chronic wounds. Methods: structure D obtained from Protein Data Bank (PDB) analyzed using UCSF Chimera. Molecular interactions ferrous ions (Fe2+) were studied, focusing on key residues (D33 D231) (E5, E180, D187). Results: Our results showed that form 96 kDa dimer, consisted heterodimers with distinct amino acid chains, where D33 D231 formed site, E5, D187 constituted zipper. A functional pocket containing conserved D231, essential proteolytic activity, identified. At pH (~7.5), exhibited most potent Fe2+, energies −7 × 1017 J at oxygen atoms carboxylate group (OD1) α-carbon (CA) atoms, whereas slightly lower −6 γ-carbon atom (CG) CA atoms. (~4), E5 primary interacting residue, shortest distance (2.69 Å), stable across several emphasizing metal binding. Conclusions: strongly influence Fe2. pH, demonstrate robust energetically efficient binding Fe2+. same time, conditions, emerges residue involved, potentially affecting D. These insights provide foundation targeting specific modulate presenting promising opportunities therapeutic aimed improving healing.

Language: Английский

Citations

0