About this Research Topic
Discovered over 40 years ago, the tumor suppressor gene TP 53 is mutated in about 50% of human cancers. In addition to its fundamental roles in modulating tumorigenesis, p53 plays important roles in modulating the pathogenesis of an array of non-cancer diseases, such as cardiovascular disease, neural degenerative disorders, inflammatory and autoimmune diseases. p53 is ubiquitously expressed in the body. As a key transcription factor controlling the expression of over 60 genes involved in various aspects of cell biology (such as apoptosis, senescence, cell cycle regulation, and maintenance of genome stability), p53 is thought to have major impacts on the physiology and/or pathophysiology virtually in all organs. In this scenario, p53 is a double-edged sword; it can act either as a guardian to repress unwanted cell proliferation and inflammation, or as an endogenous pathogenic factor by promoting age-related degenerations.
The development of small-molecule p53 activators ignites the hope of treating both cancers and non-cancer diseases by targeting p53 pharmacologically. For example, preclinical studies in various animal models have suggested that drugging the p53 pathway may represent a viable strategy to prevent the development of pathological remodeling of blood vessels (found in arterial restenosis, transplant vasculopathy, and pulmonary hypertension). On the other hand, pharmacological inhibition of p53 brings beneficial effects on neuronal damages. Nevertheless, the mechanisms of p53 actions in non-cancer diseases, and potential translational values of the small-molecule p53 activators/inhibitors in treating non-cancer diseases, are still incompletely understood. In this Research Topic, we are interested in receiving studies addressing the mechanisms of p53 actions in non-cancer diseases, and the effects of pharmacological p53 modulators on such diseases.
We welcome both Research Articles and Review Articles focusing on (1) the mechanisms of p53 actions in (but not limited to): cardiovascular diseases (including pulmonary circulation), neural degenerative disorders, inflammation and autoimmunity; and/or (2) characterization of relevant pharmacological effects of p53 modulators. We encourage studies using contemporary omics technologies to explore the mechanisms underlying the observations. Studies on pure cell biology, and studies on the discovery/development of novel p53 modulators are also welcome.
The development of small-molecule p53 activators ignites the hope of treating both cancers and non-cancer diseases by targeting p53 pharmacologically. For example, preclinical studies in various animal models have suggested that drugging the p53 pathway may represent a viable strategy to prevent the development of pathological remodeling of blood vessels (found in arterial restenosis, transplant vasculopathy, and pulmonary hypertension). On the other hand, pharmacological inhibition of p53 brings beneficial effects on neuronal damages. Nevertheless, the mechanisms of p53 actions in non-cancer diseases, and potential translational values of the small-molecule p53 activators/inhibitors in treating non-cancer diseases, are still incompletely understood. In this Research Topic, we are interested in receiving studies addressing the mechanisms of p53 actions in non-cancer diseases, and the effects of pharmacological p53 modulators on such diseases.
We welcome both Research Articles and Review Articles focusing on (1) the mechanisms of p53 actions in (but not limited to): cardiovascular diseases (including pulmonary circulation), neural degenerative disorders, inflammation and autoimmunity; and/or (2) characterization of relevant pharmacological effects of p53 modulators. We encourage studies using contemporary omics technologies to explore the mechanisms underlying the observations. Studies on pure cell biology, and studies on the discovery/development of novel p53 modulators are also welcome.
Keywords: p53, mechanism, action, cardiovascular disease, neural degenerative disorders, inflammation, autoimmunity, pharmacological effects, omics
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