Unit of Cell and Developmental Biology, Department of Biology, University of Pisa, 56126 Pisa, Italy.
Cellular Engineering Laboratory, Fondazione Pisana per la Scienza ONLUS, 56017 Pisa, Italy.
Cells. 2020 Aug 12;9(8):1893. doi: 10.3390/cells9081893.
Building and functioning of the human brain requires the precise orchestration and execution of myriad molecular and cellular processes, across a multitude of cell types and over an extended period of time. Dysregulation of these processes affects structure and function of the brain and can lead to neurodevelopmental, neurological, or psychiatric disorders. Multiple environmental stimuli affect neural stem cells (NSCs) at several levels, thus impairing the normal human neurodevelopmental program. In this review article, we will delineate the main mechanisms of infection adopted by several neurotropic pathogens, and the selective NSC vulnerability. In particular, TORCH agents, i.e., , others (including Zika virus and Coxsackie virus), Rubella virus, Cytomegalovirus, and Herpes simplex virus, will be considered for their devastating effects on NSC self-renewal with the consequent neural progenitor depletion, the cellular substrate of microcephaly. Moreover, new evidence suggests that some of these agents may also affect the NSC progeny, producing long-term effects in the neuronal lineage. This is evident in the paradigmatic example of the neurodegeneration occurring in Alzheimer's disease.
人类大脑的构建和功能需要无数分子和细胞过程的精确协调和执行，涉及多种细胞类型，并需要经过很长时间。这些过程的失调会影响大脑的结构和功能，并可能导致神经发育、神经或精神疾病。多种环境刺激会在多个层面上影响神经干细胞 (NSC)，从而破坏正常的人类神经发育程序。在这篇综述文章中，我们将阐述几种神经嗜性病原体采用的主要感染机制，以及 NSC 的选择性易感性。特别地，我们将考虑 TORCH 病原体，即单纯疱疹病毒 1 和 2、巨细胞病毒、风疹病毒、乙型肝炎病毒和丙型肝炎病毒，以及其他病原体（包括寨卡病毒和柯萨奇病毒），它们对 NSC 自我更新的破坏性影响导致神经祖细胞耗竭，这是小头畸形的细胞基础。此外，新的证据表明，其中一些病原体也可能影响 NSC 后代，在神经元谱系中产生长期影响。这在阿尔茨海默病中发生的神经退行性变的典型例子中显而易见。
