Fella Eleni, Sokratous Kleitos, Papacharalambous Revekka, Kyriacou Kyriacos, Phillips Joy, Sanderson Sam, Panayiotou Elena, Kyriakides Theodoros
Neurology Clinic A, The Cyprus Institute of Neurology and GeneticsNicosia, Cyprus.
Cyprus School of Molecular MedicineNicosia, Cyprus.
Front Mol Neurosci. 2017 May 10;10:138. doi: 10.3389/fnmol.2017.00138. eCollection 2017.
Hereditary ATTR V30M amyloidosis is a lethal autosomal dominant sensorimotor and autonomic neuropathy caused by deposition of aberrant transthyretin (TTR). Immunohistochemical examination of sural nerve biopsies in patients with amyloidotic neuropathy show co-aggregation of TTR with several proteins; including apolipoprotein E, serum amyloid P and components of the complement cascade. Complement activation and macrophages are increasingly recognized to play a crucial role in amyloidogenesis at the tissue bed level. In the current study we test the effect of two C5a receptor agonists and a C5a receptor antagonist (PMX53) on disease phenotype in ATTR V30M mice. Our results indicate that amyloid deposition was significantly reduced following treatment with the C5a receptor agonists, while treatment with the antagonist resulted in a significant increase of amyloid load. Administration of the C5a receptor agonists triggered increased recruitment of phagocytic cells resulting in clearance of amyloid deposits.
遗传性转甲状腺素蛋白（TTR）V30M淀粉样变性是一种由异常转甲状腺素蛋白（TTR）沉积引起的致死性常染色体显性感觉运动和自主神经病变。对淀粉样变性神经病患者的腓肠神经活检进行免疫组织化学检查发现，TTR与几种蛋白质共同聚集，包括载脂蛋白E、血清淀粉样蛋白P和补体级联反应的成分。补体激活和巨噬细胞在组织床水平的淀粉样变形成中发挥关键作用，这一点越来越受到认可。在本研究中，我们测试了两种C5a受体激动剂和一种C5a受体拮抗剂（PMX53）对ATTR V30M小鼠疾病表型的影响。我们的结果表明，用C5a受体激动剂治疗后淀粉样蛋白沉积显著减少，而用拮抗剂治疗则导致淀粉样蛋白负荷显著增加。给予C5a受体激动剂会引发吞噬细胞募集增加，从而清除淀粉样蛋白沉积物。
