Klegeris Andis, McGeer Patrick L
Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3.
Biochem Biophys Res Commun. 2007 Jun 15;357(4):1096-9. doi: 10.1016/j.bbrc.2007.04.055. Epub 2007 Apr 18.
Complement can damage host tissue when overactivated. Evidence of complement self damage exists for Alzheimer disease (AD), age-related macular degeneration, type 1 diabetes mellitus (T1DM), and Parkinson disease (PD). Known complement activators include Abeta, found in AD, and IgG found in T1DM. We compared their complement activating ability in vitro with those of islet amyloid polypeptide (IAPP), which aggregates in the pancreas of T2DM, and alpha-synuclein (alpha-Syn), which aggregates in PD. We found that IAPP and the alternatively spliced alpha-Syn 112 form, but not full-length alpha-Syn 140, activated complement in vitro. Complement activation may contribute to death of insulin-secreting cells in T2DM or to neuronal death in Parkinson disease (PD) and related synucleinopathies where alpha-Syn 112 occurs. This suggests the possibility of anti-inflammatory treatment in these pathologies. It also suggests that blockers of complement activation may be an appropriate therapeutic target for a range of age-related degenerative diseases.
补体过度激活时会损害宿主组织。在阿尔茨海默病（AD）、年龄相关性黄斑变性、1型糖尿病（T1DM）和帕金森病（PD）中存在补体自身损伤的证据。已知的补体激活剂包括AD中发现的β淀粉样蛋白（Aβ）和T1DM中发现的免疫球蛋白G（IgG）。我们将它们在体外的补体激活能力与胰岛淀粉样多肽（IAPP，在2型糖尿病（T2DM）的胰腺中聚集）和α-突触核蛋白（α-Syn，在PD中聚集）的补体激活能力进行了比较。我们发现IAPP和选择性剪接的α-Syn 112形式而非全长α-Syn 140在体外激活了补体。补体激活可能导致T2DM中胰岛素分泌细胞的死亡，或导致帕金森病（PD）及出现α-Syn 112的相关突触核蛋白病中的神经元死亡。这提示了在这些疾病中进行抗炎治疗的可能性。这也表明补体激活阻滞剂可能是一系列年龄相关性退行性疾病的合适治疗靶点。
