Mollica Adriano, Stefanucci Azzurra, Costante Roberto, Pinnen Francesco
University G. d'Annunzio of Chieti-Pescara, Faculty of Pharmacy; Dipartimento di Scienze del Farmaco,Via dei Vestini, 31, 66100 Chieti, Italy.
Antiinflamm Antiallergy Agents Med Chem. 2012;11(1):20-36. doi: 10.2174/187152312803476246.
Neurodegenerative disorders, such as multiple sclerosis, prion diseases, Alzheimer's disease and Parkinson's disease are often associated with inflammatory process, which involves various components of the immune system in the central nervous system, in particular astrocytes and microglial cells. Inflammation mediators such as cytokines, leukotrienes, superoxide radicals, eicosanoids, the complement cascade, and FPR agonists (formyl peptides) may play a significant role in pro-inflammatory responses, in which infiltration of activated mononuclear phagocytes at the sites of lesion is a common feature. To prevent long-term inflammation damage, the central nervous system could be treated with antinflammatory agents such as non-steroidal anti-inflammatory drugs (NSAIDs), but only few drugs were found to be effective and their therapeutic benefits is limited by side effects. Accumulating evidences suggest that targeting glia-neuron system might be a therapeutic approach in the treatment of neurodegenerative disease progression, in particular of Alzheimer's disease. Aminopyridazine derivative discovered in unbiased cell-based screens for new synthetic compounds, have proved to be able to suppress selective glial activation responses via mechanisms distinct from NSAIDs. In this review, we report the potential involvement of FPR receptors in inflammatory responses and the potential use of their antagonists to modulate the inflammatory responses of the microglia. Recent results demonstrate that targeting of inflammatory glia cytokine pathways, can suppress Aβ-induced neuroinflammation in vivo, resulting in the attenuation of neuronal damage.
神经退行性疾病，如多发性硬化症、朊病毒病、阿尔茨海默病和帕金森病，通常与炎症过程相关，这涉及中枢神经系统免疫系统的各种成分，特别是星形胶质细胞和小胶质细胞。炎症介质，如细胞因子、白三烯、超氧自由基、类花生酸、补体级联反应和FPR激动剂（甲酰肽），可能在促炎反应中起重要作用，其中病变部位活化单核吞噬细胞的浸润是一个常见特征。为了防止长期炎症损伤，中枢神经系统可以用抗炎药如非甾体抗炎药（NSAIDs）进行治疗，但只有少数药物被发现有效，并且它们的治疗益处受到副作用的限制。越来越多的证据表明，针对胶质细胞-神经元系统可能是治疗神经退行性疾病进展，特别是阿尔茨海默病的一种治疗方法。在基于细胞的无偏筛选新合成化合物中发现的氨基哒嗪衍生物，已被证明能够通过不同于NSAIDs的机制抑制选择性胶质细胞活化反应。在这篇综述中，我们报告了FPR受体在炎症反应中的潜在作用以及它们的拮抗剂调节小胶质细胞炎症反应的潜在用途。最近的结果表明，针对炎症性胶质细胞因子途径，可以在体内抑制Aβ诱导的神经炎症，从而减轻神经元损伤。
