Abstract
Effective therapies for chronic or non-healing wounds are still lacking. These tissue insults often result in severe clinical complications (i.e., infections and/or amputation) and sometimes lead to patient death. Accordingly, several research groups have focused their efforts in finding innovative and powerful therapeutic strategies to overcome these issues. On the basis of these considerations, the comprehension of the molecular cascades behind these pathological conditions could allow the identification of molecules against chronic wounds. In this context, the regulation of the Protein Kinase C (PKC) cascade has gained relevance in the prevention and/or reparation of tissue damages. This class of phosphorylating enzymes has already been considered for different physiological and pathological pathways and modulation of such enzymes may be useful in reparative processes. Herein, the recent developments in this field will be disclosed, highlighting the pivotal role of PKC α and δ in regenerative medicine. Moreover, an overview of well-established PKC ligands, acting via the modulation of these isoenzymes, will be deeply investigated. This study is aimed at re-evaluating widely known PKC modulators, currently utilized for treating other diseases, as fruitful molecules in wound-healing.
Highlights
Regenerative medicine is a multi-approach branch of translational research, involving both reparative and regenerative strategies, with the aim to restore the normal functions of damaged tissues
Drugs which benefit wound healing are of high interest to both academia and the pharmaceutical industry
The discovery of effective drugs for the treatment of chronic or non-healing lesions is still a challenge and, as illustrated throughout the present work, further studies on the mechanisms involved in wound healing are still required
Summary
Regenerative medicine is a multi-approach branch of translational research, involving both reparative and regenerative strategies, with the aim to restore the normal functions of damaged tissues. Damage triggers a series of molecular cascades that collimate into self-repair processes; lesions such as chronic or non-healing wounds (e.g., vascular insufficiency ulcers, diabetic ulcers, pressure sores and radiation necrosis) do not activate these natural reparative mechanisms [4] Such conditions often result in severe clinical complications (e.g., infections and/or amputation) and sometimes lead to patient death; regenerative medicine therapies may represent powerful strategies to circumPhvaremnacteuthticeaslse20is1s7,u1e0,s4[65]. The potential of these cells as therapeutic tool, had already brought to fibroblast transplant being proposed as part of regenerative therapy in wounded patients with interesting results [47,48] This approach was less effective in diabetic subjects, probably owing to the multiple alterations determined by diabetes itself, such as abnormal blood glucose levels, impaired Vascular Endothelial Growth Factor (VEGF) expression levels and PKC activation [49]. To stimulate the interest of medicinal chemists in developing novel selective PKC ligands, an overview of the most relevant compounds discovered so far will be discussed
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