Cianciulli Antonia, Porro Chiara, Calvello Rosa, Trotta Teresa, Lofrumento Dario Domenico, Panaro Maria Antonietta
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy.
Department of Clinical and Experimental Medicine, University of Foggia, 71100 Foggia, Italy.
Biomolecules. 2020 Jan 14;10(1):137. doi: 10.3390/biom10010137.
Immune activation in the central nervous system involves mostly microglia in response to pathogen invasion or tissue damage, which react, promoting a self-limiting inflammatory response aimed to restore homeostasis. However, prolonged, uncontrolled inflammation may result in the production by microglia of neurotoxic factors that lead to the amplification of the disease state and tissue damage. In particular, specific inducers of inflammation associated with neurodegenerative diseases activate inflammatory processes that result in the production of a number of mediators and cytokines that enhance neurodegenerative processes. Phosphoinositide 3-kinases (PI3Ks) constitute a family of enzymes regulating a wide range of activity, including signal transduction. Recent studies have focused attention on the intracellular role of PI3K and its contribution to neurodegenerative processes. This review illustrates and discusses recent findings about the role of this signaling pathway in the modulation of microglia neuroinflammatory responses linked to neurodegeneration. Finally, we discuss the modulation of PI3K as a potential therapeutic approach helpful for developing innovative therapeutic strategies in neurodegenerative diseases.
中枢神经系统中的免疫激活主要涉及小胶质细胞对病原体入侵或组织损伤的反应,小胶质细胞会做出反应,促进旨在恢复体内平衡的自限性炎症反应。然而,长期不受控制的炎症可能导致小胶质细胞产生神经毒性因子,从而导致疾病状态和组织损伤的加剧。特别是,与神经退行性疾病相关的特定炎症诱导剂会激活炎症过程,导致产生多种增强神经退行性过程的介质和细胞因子。磷酸肌醇3-激酶(PI3K)是一类调节广泛活性(包括信号转导)的酶家族。最近的研究集中在PI3K的细胞内作用及其对神经退行性过程的贡献。本综述阐述并讨论了关于该信号通路在调节与神经退行性变相关的小胶质细胞神经炎症反应中的作用的最新发现。最后,我们讨论了PI3K的调节作为一种潜在的治疗方法,有助于开发神经退行性疾病的创新治疗策略。