Lozovaya Natalya, Miller Andrew D
Department of Cellular Membranology Bogomoletz Institute of Physiology Bogomoletz Str. 4, Kiev, 01204, Ukraine.
Chembiochem. 2003 Jun 6;4(6):466-84. doi: 10.1002/cbic.200200492.
Stress is a ubiquitous and pervasive part of modern life that is frequently blamed for causing a plethora of diseases and other discomforting medical conditions. All higher organisms, including humans, experience stress in the form of a wide variety of stressors that range from environmental pollutants and drugs to traumatic events or self-induced trauma. Stressors registered by the central nervous system (CNS) generate physiological stress responses in the body (periphery) by means of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis. This LHPA axis operates through the use of chemical messengers such as the stress hormones corticotropin-releasing hormone (CRH) and glucocorticoids (GCs). Under conditions of frequent exposure to acute stress and/or chronic, long-term exposure to stress, the LHPA axis becomes dysfunctional and in the process frequently overproduces both CRH and GCs, which results in many mild to severely toxic side effects. Bidirectional communication between the LHPA axis and immune/inflammatory systems can dramatically potentiate these side effects and create environments in the CNS and periphery ripe for the triggering and/or promotion of tissue degeneration and disease. This review aims to present as far as possible a molecular view of the processes involved so as to provide a bridge from the diffuse range of studies on molecular structure and receptor interactions to the burgeoning biological and medical literature that describes the empirical interplay between stress and disease. We hope that our review of this fast-growing field, which we christen chemical neuroimmunology, will give a clear indication of the striking range and depth of current molecular, cellular and medical evidence linking stress hormones to degeneration and disease. In so doing, we hope to provide encouragement for others to become interested in this critical and far-reaching field of research, which is very much at the heart of many important disease processes and very much a critical part of the crucial interface between chemistry and biology.
压力是现代生活中普遍存在且无所不在的一部分，人们常常将众多疾病和其他令人不适的健康状况归咎于它。所有高等生物，包括人类，都会以各种各样的应激源的形式体验压力，这些应激源从环境污染物、药物到创伤性事件或自我诱发的创伤不等。中枢神经系统（CNS）所记录的应激源通过边缘 - 下丘脑 - 垂体 - 肾上腺（LHPA）轴在身体（外周）产生生理应激反应。这个LHPA轴通过使用化学信使来运作，比如应激激素促肾上腺皮质激素释放激素（CRH）和糖皮质激素（GCs）。在频繁暴露于急性应激和/或长期、慢性暴露于应激的情况下，LHPA轴会功能失调，在此过程中常常会过度产生CRH和GCs，这会导致许多从轻到重的毒性副作用。LHPA轴与免疫/炎症系统之间的双向通信会极大地增强这些副作用，并在中枢神经系统和外周创造出有利于引发和/或促进组织退化和疾病的环境。本综述旨在尽可能呈现所涉及过程的分子视角，以便搭建一座桥梁，将关于分子结构和受体相互作用的广泛研究与描述应激和疾病之间实证相互作用的新兴生物学和医学文献联系起来。我们希望我们对这个快速发展的领域（我们将其命名为化学神经免疫学）的综述，能够清楚地表明当前将应激激素与退化和疾病联系起来的分子、细胞和医学证据的显著范围和深度。通过这样做，我们希望鼓励其他人对这个至关重要且影响深远的研究领域产生兴趣，这个领域处于许多重要疾病过程的核心，并且是化学与生物学关键界面的重要组成部分。
