Year: 2024
Type: editorial
Abstract: Autophagy, a vital cellular process responsible for maintaining homeostasis by degrading and recycling cellular components, has emerged as a critical area of research in recent years (1)(2)(3)(4)(5). This intricate mechanism plays a dual role in health and disease, safeguarding cellular function while also contributing to the pathology of various conditions. This special issue explores the complexities of autophagy, shedding light on its diverse roles across a spectrum of diseases, including chronic obstructive pulmonary disease (COPD), rotator cuff injuries, bile duct carcinoma, and Alzheimer's disease. The featured studies provide fresh insights into the protective and potentially harmful aspects of autophagy, offering new avenues for therapeutic intervention and advancing our understanding of its role in disease progression.In the intricate web of cellular homeostasis, autophagy and oxidative stress are two fundamental players that maintain equilibrium. COPD is a progressive respiratory condition characterized by persistent inflammation and oxidative stress, leading to irreversible airflow limitation (6). In this review, Zhao et al. (Front Physiol. 2022 Sep 26;13:1004275) illuminated the nuanced interplay between these processes and their roles in COPD pathogenesis. Oxidative stress results from an imbalance between reactive oxygen species (ROS) and the body's ability to detoxify them, leading to cellular damage and inflammation. Autophagy, a cellular process responsible for degrading and recycling damaged organelles and proteins, plays a dual role in COPD. On one hand, autophagy helps mitigate oxidative stress by removing damaged mitochondria, which are significant sources of ROS. On the other hand, chronic oxidative stress can impair autophagic processes, leading to the accumulation of damaged cellular components. This disruption contributes to the progression of COPD by promoting inflammation and cellular senescence. Recent insights into this interplay underscore the potential of targeting autophagy pathways as a therapeutic strategy to mitigate oxidative stress and improve outcomes in COPD patients.Rotator cuff injuries, particularly chronic enthesis tears, pose significant challenges in orthopedic medicine. Enthesis refers to the site where tendons or ligaments attach to bone, and tears at these sites can lead to debilitating pain and functional impairment. The pathology of these injuries is increasingly recognized to involve oxidative stress and autophagy (7). Oxidative stress in rotator cuff tears results from the excessive production of ROS and impaired antioxidant defenses. This imbalance damages cellular components and contributes to inflammation and tissue degeneration. Autophagy in this context appears to be a double-edged sword. While autophagy can help remove damaged cells and repair tissues, excessive or dysregulated autophagy may exacerbate tissue damage and inflammation. The challenge in treating chronic rotator cuff tears lies in modulating autophagy to promote healing while minimizing oxidative stress-induced damage. Additionally, the study examined autophagy's role in chemoresistance in breast cancer. It was found that dihydroartemisinin and artesunate could reverse doxorubicin resistance by inducing autophagy, as indicated by increased levels of LC3B and ATG7. This research highlights the intricate role of autophagy in cancer and its potential as a therapeutic target for improving treatment outcomes and overcoming drug resistance.Barmaki et al. (Frontiers in Aging Neuroscience, November 2023) reviewed the critical role of autophagy dysfunction in Alzheimer's disease (AD). Autophagy, a key cellular process for maintaining protein balance and organelle health, is disrupted in AD, leading to the accumulation of amyloid-beta plaques, tau tangles, and damaged organelles-core features of the disease.The review emphasizes the complex interactions between autophagy and other cellular systems, such as mitochondrial function and endoplasmic reticulum stress. Dysfunction in these interconnected pathways further exacerbates the progression of AD. For instance, impaired autophagy can contribute to mitochondrial dysfunction, increasing oxidative stress and cellular damage. Effective AD therapies may need to address these related systems alongside autophagy.Genetic and environmental factors influencing autophagy also impact AD susceptibility.Variations in genes encoding autophagic proteins have been linked to an increased risk of the disease, suggesting that understanding these genetic factors could help in identifying at-risk individuals and tailoring preventative strategies.Recent advances in autophagy-modulating drugs show potential for AD treatment by enhancing protein clearance and reducing neurotoxic aggregates in preclinical models. However, translating these findings into clinical practice requires careful evaluation of drug dosing, safety, and long-term efficacy. The study advocates for continued research and clinical trials to optimize autophagy-based therapies for AD.Overall, targeting autophagy mechanisms holds promise for developing new therapeutic strategies to slow or potentially halt the progression of Alzheimer's disease.The papers in this special issue explore the critical role of autophagy in COPD, rotator cuff injuries, bile duct carcinoma, and Alzheimer's disease, highlighting its dual nature as both a protector and potential contributor to disease. While these studies provide valuable insights, they represent just a fraction of the broader spectrum of conditions in which autophagy dysregulation plays a key role, including adverse pregnancy outcomes, renal and cardiovascular diseases, diabetes, and obesity (1)(2)(3)(4)(5). The intricate balance of autophagic activity is essential for maintaining health. As we gain a deeper understanding of autophagy's multifaceted roles, new therapeutic avenues are emerging, offering hope for more effective treatments across various medical fields.However, the real challenge lies in precisely modulating autophagy to maximize its benefits while avoiding the risk of exacerbating disease. This underscores the need for continued research and innovation in this dynamic and rapidly evolving area of study.Autophagy, chronic obstructive pulmonary disease, Alzheimer's disease, rotator cuff injuries, bile duct carcinoma, oxidative stress
Source: Frontiers in Physiology
Authors: Shibin Cheng, Xiaodi Chen, Aihua Liao
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,295
OpenAlex ID: W4403003895