Kostrzewa Richard M, Segura-Aguilar Juan
Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Neurotox Res. 2003;5(6):375-83. doi: 10.1007/BF03033166.
Cellular mechanisms involved in neurodegeneration and neuroprotection are continuing to be explored, and this paper focuses on some novel discoveries that give further insight into these processes. Oligodendrocytes and activated astroglia are likely generators of the pro-inflammatory cytokines, such as the tumor necrosis factor family and interleukin family, and these glial support cells express adhesion receptors (e.g., VCAM) and release intercellular adhesion molecules (ICAM) that have a major role in neuronal apoptosis. Even brief exposure to some substances, in ontogeny and sometimes in adulthood, can have lasting effects on behaviors because of their prominent toxicity (e.g., NMDA receptor antagonists) or because they sensitize receptors (e.g., dopamine D2 agonists), possibly permanently, and thereby alter behavior for the lifespan. Cell cycle genes which may be derived from microglia, are the most-recent entry into the neuroprotection schema. Neuroprotection afforded by some common substances (e.g., melatonin) and uncommon substances [e.g., nicotine, green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG), trolox], ordinarily thought to be simple radical scavengers, now are thought to invoke previously unsuspected cellular mechanisms in the process of neuroprotection. Although Alzheimer's disease (AD) has features of a continuous spectrum of neural and functional decline, in vivo PET imaging and and functional magnetic resonance imaging, indicate that AD can be staged into an early phase treatable by inhibitors of beta and gamma secretase; and a late phase which may be more amenable to treatment by drugs that prevent or reverse tau phosphorylation. Neural transplantation, thought to be the last hope for neurally injured patients (e.g., Parkinsonians), may be displaced by non-neural tissue transplants (e.g., human umbilical cord blood; Sertoli cells) which seem to provide similar neurotrophic support and improved behavior - without posing the major ethical dilemma of removing tissue from aborted fetuses. The objective of this paper is to invite added research into the newly discovered (or postulated) novel mechanisms; and to stimulate discovery of additional mechanisms attending neurodegeneration and neuroprotection.
参与神经退行性变和神经保护的细胞机制仍在不断探索中，本文重点关注一些新发现，这些发现能让我们对这些过程有更深入的了解。少突胶质细胞和活化的星形胶质细胞可能是促炎细胞因子的产生者，如肿瘤坏死因子家族和白细胞介素家族，这些神经胶质支持细胞表达黏附受体（如血管细胞黏附分子）并释放细胞间黏附分子，它们在神经元凋亡中起主要作用。即使在个体发育过程中，有时在成年期，短暂接触某些物质也会因其显著的毒性（如N-甲基-D-天冬氨酸受体拮抗剂）或因其使受体敏感化（如多巴胺D2激动剂）而对行为产生持久影响，这种影响可能是永久性的，从而在整个生命周期中改变行为。可能源自小胶质细胞的细胞周期基因是神经保护模式中的最新成员。一些常见物质（如褪黑素）和不常见物质[如尼古丁、绿茶多酚（-）-表没食子儿茶素-3-没食子酸酯（EGCG）、生育三烯酚]通常被认为只是简单的自由基清除剂，现在认为它们在神经保护过程中会引发以前未被怀疑的细胞机制，从而提供神经保护作用。尽管阿尔茨海默病（AD）具有神经和功能持续衰退的特征，但体内正电子发射断层扫描（PET）成像和功能磁共振成像表明，AD可分为早期，可用β和γ分泌酶抑制剂治疗；以及晚期，可能更适合用预防或逆转tau蛋白磷酸化的药物治疗。神经移植曾被认为是神经损伤患者（如帕金森病患者）的最后希望，但可能会被非神经组织移植（如人脐带血；支持细胞）所取代，这些非神经组织移植似乎能提供类似的神经营养支持并改善行为，同时不会带来从流产胎儿获取组织所带来的重大伦理困境。本文的目的是呼吁对新发现（或假设）的新机制进行更多研究，并刺激发现更多与神经退行性变和神经保护相关的机制。
