Department of Neuroimmunology, European Graduate School of Neuroscience, Biomedical Research Institute, Hasselt University, Hasselt, Belgium.
Department Psychiatry and Neuropsychology, European Graduate School of Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
Front Immunol. 2019 Jul 24;10:1727. doi: 10.3389/fimmu.2019.01727. eCollection 2019.
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) characterized by heterogeneous clinical symptoms including gradual muscle weakness, fatigue, and cognitive impairment. The disease course of MS can be classified into a relapsing-remitting (RR) phase defined by periods of neurological disabilities, and a progressive phase where neurological decline is persistent. Pathologically, MS is defined by a destructive immunological and neuro-degenerative interplay. Current treatments largely target the inflammatory processes and slow disease progression at best. Therefore, there is an urgent need to develop next-generation therapeutic strategies that target both neuroinflammatory and degenerative processes. It has been shown that elevating second messengers (cAMP and cGMP) is important for controlling inflammatory damage and inducing CNS repair. Phosphodiesterases (PDEs) have been studied extensively in a wide range of disorders as they breakdown these second messengers, rendering them crucial regulators. In this review, we provide an overview of the role of PDE inhibition in limiting pathological inflammation and stimulating regenerative processes in MS.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性脱髓鞘疾病，其特征是具有不同的临床症状，包括逐渐出现的肌肉无力、疲劳和认知障碍。MS 的疾病过程可分为复发缓解（RR）期和进行性期，前者表现为神经功能障碍，后者则表现为神经衰退持续存在。从病理学上看，MS 是由破坏性的免疫和神经退行性相互作用定义的。目前的治疗方法主要针对炎症过程，并在最佳情况下减缓疾病进展。因此，迫切需要开发新一代的治疗策略，以针对神经炎症和退行性过程。已经表明，提高第二信使（cAMP 和 cGMP）对于控制炎症损伤和诱导中枢神经系统修复非常重要。磷酸二酯酶（PDEs）在广泛的疾病中被广泛研究，因为它们分解这些第二信使，使其成为关键的调节剂。在这篇综述中，我们概述了 PDE 抑制在限制 MS 中的病理性炎症和刺激再生过程中的作用。
