Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection. A review.
Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection. A review.
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DOI：
10.1007/bf03033166
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发表时间：
2003-01-01
影响因子：
3.7
通讯作者：
Segura-Aguilar, J
中科院分区：
文献类型：
--
作者：
Kostrzewa, RM;Segura-Aguilar, J
参与神经变性和神经保护的细胞机制仍在探索中，本文重点介绍了一些新的发现，进一步了解这些过程。少突胶质细胞和活化的星形胶质细胞可能是促炎性细胞因子如肿瘤坏死因子家族和白细胞介素家族的产生者，并且这些胶质支持细胞表达粘附受体（例如，VCAM）并释放在神经元凋亡中起主要作用的细胞间粘附分子（ICAM）。即使在个体发育中，有时在成年期短暂接触某些物质，也会对行为产生持久的影响，因为它们具有显著的毒性（例如，NMDA受体拮抗剂）或因为它们敏化受体（例如，多巴胺D-2激动剂），可能是永久性的，从而改变行为的寿命。细胞周期基因可能来源于小胶质细胞，是最近进入神经保护模式。一些常见物质提供的神经保护（例如，褪黑激素）和不常见的物质[例如，尼古丁、绿色茶多酚（-）-表没食子儿茶素-3-没食子酸酯（EGCG）、trolox]，通常被认为是简单的自由基清除剂，现在被认为在神经保护过程中引起先前未被怀疑的细胞机制。虽然阿尔茨海默病（AD）具有神经和功能下降的连续谱的特征，但体内PET成像和功能性磁共振成像表明AD可以分阶段进入可通过β和γ分泌酶抑制剂治疗的早期阶段;以及可能更适合通过预防或逆转tau磷酸化的药物治疗的晚期阶段。神经移植，被认为是神经损伤患者的最后希望（例如，帕金森病患者），可能会被非神经组织移植（例如，人脐带血;支持细胞），这似乎提供了类似的神经营养支持和改善行为-没有造成主要的道德困境，从流产胎儿切除组织。本文的目的是邀请更多的研究新发现（或假设）的新机制，并刺激发现其他机制参加神经变性和神经保护。
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 D-2 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.