Darwish Radwan, Alcibahy Yasmine, Bucheeri Shahd, Albishtawi Ashraf, Tama Maya, Shetty Jeevan, Butler Alexandra E
School of Medicine, Royal College of Surgeons in Ireland-Medical University of Bahrain (RCSI-MUB), Busaiteen 228, Bahrain.
Department of Biochemistry, Royal College of Surgeons in Ireland-Medical University of Bahrain (RCSI-MUB), Busaiteen 228, Bahrain.
Int J Mol Sci. 2024 Dec 7;25(23):13169. doi: 10.3390/ijms252313169.
Historically, microglial activation has been associated with diseases of a neurodegenerative and neuroinflammatory nature. Some, like Alzheimer's disease, Parkinson's disease, and multiple system atrophy, have been explored extensively, while others pertaining to metabolism not so much. However, emerging evidence points to hypothalamic inflammation mediated by microglia as a driver of metabolic dysregulations, particularly insulin resistance and type 2 diabetes mellitus. Here, we explore this connection further and examine pathways that underlie this relationship, including the IKKβ/NF-κβ, IRS-1/PI3K/Akt, mTOR-S6 Kinase, JAK/STAT, and PPAR-γ signaling pathways. We also investigate the role of non-coding RNAs, namely microRNAs and long non-coding RNAs, in insulin resistance related to neuroinflammation and their diagnostic and therapeutic potential. Finally, we explore therapeutics further, searching for both pharmacological and non-pharmacological interventions that can help mitigate microglial activation.
从历史上看，小胶质细胞激活一直与神经退行性和神经炎症性疾病相关。其中一些疾病，如阿尔茨海默病、帕金森病和多系统萎缩，已经得到了广泛研究，而其他与代谢相关的疾病则研究较少。然而，新出现的证据表明，小胶质细胞介导的下丘脑炎症是代谢失调的驱动因素，特别是胰岛素抵抗和2型糖尿病。在这里，我们进一步探讨这种联系，并研究构成这种关系基础的途径，包括IKKβ/NF-κβ、IRS-1/PI3K/Akt、mTOR-S6激酶、JAK/STAT和PPAR-γ信号通路。我们还研究非编码RNA，即微小RNA和长链非编码RNA，在与神经炎症相关的胰岛素抵抗中的作用及其诊断和治疗潜力。最后，我们进一步探索治疗方法，寻找有助于减轻小胶质细胞激活的药理学和非药理学干预措施。
Zotero 插件
