Zsuzsa Muszka 1,2,4 , Viktória Jenei1,3,4, Rebeka Mácsik1 , Evgeniya Mezhonova1 , Silina Diyab1 , Réka Csősz1 , Attila Bácsi1 , Anett Mázló1✉ and Gábor Koncz 1 ✉
Chronic diseases affecting the cardiovascular system, diabetes mellitus, neurodegenerative diseases, and various other organspecific conditions, involve different underlying pathological processes. However, they share common risk factors that contribute to the development and progression of these diseases, including air pollution, hypertension, obesity, high cholesterol levels, smoking and alcoholism. In this review, we aim to explore the connection between four types of diseases with different etiologies and various risk factors. We highlight that the presence of risk factors induces regulated necrotic cell death, leading to the release of damage-associated molecular patterns (DAMPs), ultimately resulting in sterile inflammation. Therefore, DAMP-mediated inflammation may be the link explaining how risk factors can lead to the development and maintenance of chronic diseases. To explore these processes, we summarize the main cell death pathways activated by the most common life-threatening risk factors, the types of released DAMPs and how these events are associated with the pathophysiology of diseases with the highest mortality.
Cell Death and Disease (2025) 16:273 ; https://doi.org/10.1038/s41419-025-07563-7
FACTS
Environmental, physiological or behavioral risk factors can induce regulated necrotic cell death and DAMP production.
DAMP-related sterile inflammation plays a role in the development and progression of cardiovascular diseases, neurodegenerative diseases, diabetes or alcoholic and non-alcoholic liver diseases.
Current anti-inflammatory treatments do not target the root cause of cell death processes and the release of DAMPs.
OPEN QUESTIONS
To what extent can the harmful effects of risk factors be mitigated by regulating necrotic cell death?
To what extent do the DAMP patterns of pathologies associated with sterile inflammation overlap?
In which diseases can drugs targeting the pathomechanism ofsterile inflammation be used, such as drugs that inhibit the effects of regulated cell death or DAMPs?
1 Department of Immunology, Faculty of Medicine, University of Debrecen, Egyetem square 1, 4032 Debrecen, Hungary. 2 Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Egyetem square 1, 4032 Debrecen, Hungary. 3 Gyula Petrányi Doctoral School of Allergy and Clinical Immunology, University of Debrecen, Egyetem square 1, 4032 Debrecen, Hungary. 4 These authors contributed equally: Zsuzsa Muszka, Viktória Jenei. ✉email: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 Edited By Massimiliano Agostini
Brigitte DRÉNO1 Isabelle BENOIT2 Eric PERRIER2 Miroslav RADMAN3
1 INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302/EMR6001, Nantes Université, Nantes, France
2 NAOS-ILS, Aix-en-Provence, France,
3 Mediterranean Institute for Life Sciences, Split, Croatia, Naos Institute for Life Sciences, Aix-en-Provence, France, Université R.-Descartes Paris-5, Faculté de Médecine, INSERM U1, Paris, France
Reprints: Brigitte Dréno<该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。> <该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。>
Isabelle Benoit <该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。>
Eric Perrier <该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。>
Skin aging is associated with a progressive decline in physiological functions, skin cancers and, ultimately, death. It may be categorized as intrinsic or extrinsic, whereby intrinsic aging is attributed to chrono-logical and genetic factors. At the molecular level, skin aging involves changes in protein conformation and function. The skin proteome changes constantly, mainly through carbonylation; an irreversible phenomenon leading to protein accumulation as toxic aggregates that impair cellular physiology and accelerate skin aging. This review details the central role of proteostasis during skin aging and why proteome protection may be a promising approach in mitigating skin aging. A comprehensive literature review of 87 articles focusing on the proteome, proteostasis, proteotoxicity, protein carbonylation, and the impact of the damaged proteome on aging, and in particular skin aging, was conducted. Skin aging is associated with deficiencies in the repair mechanisms of DNA, transcriptional control, mitochondrial function, cell cycle control, apoptosis, cellular metabolism, changes in hormonal levels secondary to toxicity of damaged proteins, and cell-to-cell communication for tissue homeostasis, which are largely controlled by proteins. In this context, a damaged proteome that leads to the loss of proteostasis may be considered as the first step in tissue aging. There is growing evidence that a healthy proteome plays a central role in skin and in maintaining healthy tissues, thus slow-ing down the process of skin aging. Hence, protecting the proteome against oxidative or other damage may be an appropriate strategy to prevent and delay skin aging.
Keywords: proteome, proteostasis, protein carbonylation, skin aging
现任中华医学会创伤分会创面学组全国委员、中国医师学会烧伤分会全国委员、中华医学会烧伤分会青年委员、全军烧伤专业委员会委员、重庆市烧伤专业委员会委员、西南五省一巿烧伤整形学术委员会常委、中华烧伤杂志通讯编委、国家自然基金及SFDA新药评审专家、国外SCI杂志BURNS及Military Medicine等杂志审稿人等。
教授,烧伤科主任,博士生导师,国家级首批新世纪百千万人才工程人选、省烧伤外科专业委员会常委等。享受国务院特殊津贴。
管理治疗了大量烧烫伤、冻伤、电击伤、压疮及瘢痕患者,多次参与成批危重烧伤患者的救治工作。曾于国内外多所权威激光及整形治疗机构进修学习。
擅长: 各种烧伤治疗、表皮肿物去除和皮瓣成形、体表瘢痕防治,糖尿病足、褥疮、慢性难愈性创面的治疗;面部、胸部整形,自体脂肪移植。
从事整形、烧伤临床、教学、科研10年。2016年在中国科学院整形外科医院进修整1年,系统的学习了整形美容理论知识和临床手术技能。在国内第一作者发表论文6篇,参与发表论文20余篇,多篇为核心期刊。
伤口世界平台生态圈,以“关爱人间所有伤口患者”为愿景,连接、整合和拓展线上和线下的管理慢性伤口的资源,倡导远程、就近和居家管理慢性伤口,解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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