Apoptosis: A Friend Or Foe?

Nilesh M. Pandya; Sunita M. Jain; Dev D. Santani

摘要

Over the past several years, a growing number of researchers have become fascinated with apoptosis, a form of programmed cell death, and it is now widely accepted that this physiological cell death is a fundamental feature of life. The reason why apoptosis research has experienced such a rapid development relates to its biological relevance. Apoptosis is the physiological way for nucleated cells to die. Apoptosis takes care of unwanted, injured, or virus-infected cells. Auto reactive T and B cells, millions of which are produced by the immune system every day, are also eliminated by apoptosis. Recently, dysregulation ("too much or too little") of apoptosis has emerged as a new concept to explain important features in the development of several as yet poorly understood diseases. Unregulated excessive apoptosis may be the cause of various degenerative and autoimmune diseases that are characterized by an excessive loss of normal or protective cells, such as in multiple sclerosis, type-I diabetes mellitus, Hashimoto thyroiditis, Sjo¨gren syndrome, and certain cancers such as melanoma. Conversely, an inappropriately low rate of apoptosis may promote survival and accumulation of abnormal cells that can give rise to tumor formation and prolonged autoimmune stimulation such as in cancers and Graves disease. With the dawning of the 'age of apoptosis', substantial progress has been made in understanding the molecular cell biological mechanisms that underlie the initiation, execution and regulation of this cell death program. It seems likely that pro- and anti-apoptotic factors determine either susceptibility or resistance to apoptosis, and, consequently, play a crucial role in the evolution, propagation, and chronicity of degenerative, cancerous, and autoimmune conditions. Thus, precise identification of the distinct errors in the complex apoptotic machinery holds great promise for elucidating the pathogenesis of various important diseases and for devising more specific and effective treatments. Introduction Control of cell proliferation, differentiation, activation and cell removal is crucial for the development and existence of multicellular organisms. Each cell cycle progression, with sequences of DNA replication, mitosis, and cell division, is a tightly controlled and complicated process that, when deregulated, may become dangerous not only to a single cell, but also to the whole organism. Regulation and the proper control of the cell cycle and of programmed cell death are therefore essential for mammalian development and the homeostasis of the immune system. The molecular networks that regulate these processes are critical targets for drug development, gene therapy, and metabolic engineering. In addition to the primary, intracellular apoptotic suicide machinery, components of the immune system can detect and remove cells and tissue fragments that no longer serve their defined functions. There are two major mechanisms of cell death-necrosis and apoptosis. Cells that are damaged by external injury undergo necrosis, while cells that are induced to commit programmed suicide because of internal or external stimuli undergo apoptosis. Apoptosis, derived from the Greek word for a natural process of leaves falling from trees. Apoptosis, or programmed cell death, is a major control mechanism by which cells die if DNA damage is not repaired. Apoptosis is also important in controlling cell number and proliferation as part of normal development. The apoptosis process can be divided into at least three functionally distinct phases: initiation, effector and degradation. During the heterogeneous initiation phase, cells receive death-inducing signals: lack of obligatory survival factors, shortage of metabolite supply, ligation of death-signal transmitting receptors, subnecrotic damage by toxins, heat or irradiation. During the effector phase, these signals are translated into metabolic reactions and the decision to die is taken. The ultimate fa

机译：在过去的几年中，越来越多的研究人员着迷于程序性细胞死亡的一种形式的细胞凋亡，现在人们普遍认为这种生理性细胞死亡是生命的基本特征。细胞凋亡研究经历了如此迅速的发展的原因与其生物学相关性。凋亡是有核细胞死亡的生理途径。凋亡负责处理不需要的，受伤的或感染了病毒的细胞。每天也会由免疫系统产生数百万的自身反应性T和B细胞，也可以通过细胞凋亡消除。最近，细胞凋亡的失调（“太多或太少”）已经出现，作为一种新概念来解释几种尚不为人所知的疾病的发展中的重要特征。无节制的过度凋亡可能是各种变性和自身免疫性疾病的原因，这些疾病的特征是正常或保护性细胞的过度丧失，例如多发性硬化症，I型糖尿病，桥本甲状腺炎，干燥综合征以及某些癌症，例如作为黑色素瘤。相反，凋亡率过低可能会促进异常细胞的存活和积累，从而导致肿瘤的形成和长期的自身免疫刺激，例如在癌症和格雷夫斯病中。随着“细胞凋亡时代”的到来，在理解构成该细胞死亡程序的起始，执行和调节的分子细胞生物学机制方面取得了实质性进展。促凋亡因子和抗凋亡因子似乎决定了对凋亡的易感性或抗性，因此，在变性，癌性和自身免疫性疾病的演变，繁殖和慢性中起着至关重要的作用。因此，对复杂凋亡机制中不同错误的精确鉴定为阐明各种重要疾病的发病机理和设计更具体有效的治疗方法具有广阔的前景。简介控制细胞增殖，分化，活化和去除细胞对于多细胞生物的发展和生存至关重要。每个细胞周期的进展，以及DNA复制，有丝分裂和细胞分裂的序列，都是一个严密控制和复杂的过程，一旦失控，不仅可能对单个细胞而且对整个生物都具有危险。因此，对细胞周期和程序性细胞死亡的调节和适当控制对于哺乳动物的发育和免疫系统的体内平衡至关重要。调节这些过程的分子网络是药物开发，基因治疗和代谢工程的关键目标。除了主要的细胞内凋亡性自杀机制外，免疫系统的组件还可以检测并去除不再发挥其定义功能的细胞和组织片段。细胞死亡坏死和凋亡有两种主要机制。被外部损伤破坏的细胞会发生坏死，而由于内部或外部刺激而被诱导进行程序性自杀的细胞会发生凋亡。细胞凋亡，源自希腊语，指从树上掉下来的叶子的自然过程。凋亡或程序性细胞死亡是一种主要的控制机制，如果DNA损伤无法修复，细胞将通过这种机制死亡。凋亡对于控制细胞数量和增殖也很重要，这是正常发育的一部分。凋亡过程可分为至少三个功能上不同的阶段：起始，效应子和降解。在异质起始阶段，细胞接收诱导死亡的信号：缺乏强制性生存因子，代谢物供应不足，死亡信号传递受体的连接，毒素，热或辐射引起的坏死性损害。在效应器阶段，这些信号被转化为代谢反应，并做出死亡决定。终极fa

Apoptosis: A Friend Or Foe?

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