UK Dementia Research Institute, Department of Clinical Neurosciences, University of Cambridge, Hills Road, Cambridge CB2 0AH, UK.
U.P Medicina, Facultad de Ciencias de la Salud, Universitat Jaume I, Avda. de Vicent Sos Baynat s/n, 12071 Castelló de la Plana, Spain.
Int J Mol Sci. 2020 Jun 23;21(12):4471. doi: 10.3390/ijms21124471.
The signaling pathway of the microtubule-associated protein kinase or extracellular regulated kinase (MAPK/ERK) is a common mechanism of extracellular information transduction from extracellular stimuli to the intracellular space. The transduction of information leads to changes in the ongoing metabolic pathways and the modification of gene expression patterns. In the central nervous system, ERK is expressed ubiquitously, both temporally and spatially. As for the temporal ubiquity, this signaling system participates in three key moments: (i) Embryonic development; (ii) the early postnatal period; and iii) adulthood. During embryonic development, the system is partly responsible for the patterning of segmentation in the encephalic vesicle through the FGF8-ERK pathway. In addition, during this period, ERK directs neurogenesis migration and the final fate of neural progenitors. During the early postnatal period, ERK participates in the maturation process of dendritic trees and synaptogenesis. During adulthood, ERK participates in social and emotional behavior and memory processes, including long-term potentiation. Alterations in mechanisms related to ERK are associated with different pathological outcomes. Genetic alterations in any component of the ERK pathway result in pathologies associated with neural crest derivatives and mental dysfunctions associated with autism spectrum disorders. The MAP-ERK pathway is a key element of the neuroinflammatory pathway triggered by glial cells during the development of neurodegenerative diseases, such as Parkinson's and Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis, as well as prionic diseases. The process triggered by MAPK/ERK activation depends on the stage of development (mature or senescence), the type of cellular element in which the pathway is activated, and the anatomic neural structure. However, extensive gaps exist with regards to the targets of the phosphorylated ERK in many of these processes.
微管相关蛋白激酶或细胞外调节激酶（MAPK/ERK）的信号通路是细胞外刺激向细胞内传递信息的一种常见机制，信息传递导致正在进行的代谢途径发生变化，并修饰基因表达模式。在中枢神经系统中，ERK 时空广泛表达。就时间普遍性而言，该信号系统参与三个关键时刻：（i）胚胎发育；（ii）出生后早期；和（iii）成年期。在胚胎发育过程中，该系统通过 FGF8-ERK 途径部分负责脑泡的节段模式形成。此外，在此期间，ERK 指导神经发生迁移和神经前体细胞的最终命运。在出生后早期，ERK 参与树突棘和突触发生的成熟过程。在成年期，ERK 参与社交和情绪行为以及记忆过程，包括长时程增强。与 ERK 相关的机制改变与不同的病理结果有关。ERK 通路的任何成分的遗传改变都会导致与神经嵴衍生物相关的病理和与自闭症谱系障碍相关的精神功能障碍。MAP-ERK 通路是神经胶质细胞在神经退行性疾病（如帕金森病和阿尔茨海默病、亨廷顿病和肌萎缩侧索硬化症以及朊病毒病）发展过程中触发的神经炎症途径的关键组成部分。MAPK/ERK 激活触发的过程取决于发育阶段（成熟或衰老）、通路被激活的细胞元素类型以及解剖学神经结构。然而，在许多这些过程中，磷酸化 ERK 的靶点存在广泛的差距。
