Department of Pharmacology and Physiology, College of Medicine, Drexel University, Philadelphia, PA 19102, United States.
Department of Pharmacology and Physiology, College of Medicine, Drexel University, Philadelphia, PA 19102, United States.
Brain Res. 2019 Jan 1;1702:46-53. doi: 10.1016/j.brainres.2018.03.009. Epub 2018 Mar 22.
The evolution of peptidergic signaling systems in the central nervous system serves a distinct and crucial role in brain processes and function. The diversity of physiological peptides and the complexity of their regulation and secretion from the dense core vesicles (DCV) throughout the brain is a topic greatly in need of investigation, though recent years have shed light on cellular and molecular mechanisms that are summarized in this review. Here, we focus on the convergence of peptidergic systems onto the Locus Coeruleus (LC), the sole provider of norepinephrine (NE) to the cortex and hippocampus, via large DCV. As the LC-NE system is one of the first regions of the brain to undergo degeneration in Alzheimer's Disease (AD), and markers of DCV have consistently been demonstrated to have biomarker potential for AD progression, here we summarize the current literature linking the LC-NE system with DCV dysregulation and Aβ peptides. We also include neuroanatomical data suggesting that the building blocks of senile plaques, Aβ monomers, may be localized to DCV of the LC and noradrenergic axon terminals of the prefrontal cortex. Finally, we explore the putative consequences of chronic stress on Aβ production and the role that DCV may play in LC degeneration. Clinical data of immunological markers of DCV in AD patients are discussed.
中枢神经系统中肽能信号系统的进化在大脑过程和功能中起着独特而关键的作用。生理肽的多样性及其在大脑中从致密核心囊泡 (DCV) 中调节和分泌的复杂性是一个急需研究的课题，尽管近年来已经揭示了细胞和分子机制，本文对此进行了总结。在这里，我们专注于肽能系统汇聚到蓝斑 (LC) 的情况，LC 是向皮质和海马体提供去甲肾上腺素 (NE) 的唯一来源，通过大的 DCV。由于 LC-NE 系统是大脑中最早发生退行性变的区域之一，并且 DCV 的标志物一直被证明具有 AD 进展的生物标志物潜力，因此我们总结了目前将 LC-NE 系统与 DCV 失调和 Aβ 肽联系起来的文献。我们还包括神经解剖学数据表明，老年斑的组成部分，即 Aβ 单体，可能定位于 LC 的 DCV 和前额叶皮质的去甲肾上腺素能轴突末梢。最后，我们探讨了慢性应激对 Aβ 产生的可能影响以及 DCV 在 LC 退化中的作用。还讨论了 AD 患者 DCV 的免疫标志物的临床数据。
