Dudek S M, Johnson G V
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham 35294-0017.
Brain Res. 1994 Jul 18;651(1-2):129-33. doi: 10.1016/0006-8993(94)90688-2.
One of the major pathological characteristics of Alzheimer's disease is the increased number of amyloid-containing senile plaques within the brain. The dense cores of these plaques are composed primarily of highly insoluble aggregates of a 39-43-residue peptide referred to as the beta-amyloid peptide (beta A). The mechanisms by which these insoluble extracellular deposits of beta A are formed remain unknown. In this study, the cross-linking of beta A by the calcium-dependent enzyme, transglutaminase was examined. Transglutaminases are a family of enzymes which are found in brain, and catalyse the cross-linking of specific proteins into insoluble polymers. Synthetic beta A (1-40) was readily cross-linked by transglutaminase, forming multimers in a time-dependent fashion. Furthermore, a second peptide with a substitution similar to that in the Dutch-type hereditary amyloidosis mutation (Glu22 to Gln) was also found to be a substrate for transglutaminase. Since transglutaminase covalently cross-links proteins through glutamine residues, it is suggested that transglutaminase contributes to amyloid deposition in Dutch-type hereditary amyloidosis, and possibly Alzheimer's disease.
阿尔茨海默病的主要病理特征之一是大脑中含淀粉样蛋白的老年斑数量增加。这些斑块的致密核心主要由一种39至43个氨基酸残基的肽高度不溶性聚集体组成，该肽被称为β-淀粉样肽（βA）。βA这些不溶性细胞外沉积物形成的机制仍然未知。在本研究中，研究了钙依赖性酶转谷氨酰胺酶对βA的交联作用。转谷氨酰胺酶是一类存在于大脑中的酶，可催化特定蛋白质交联成不溶性聚合物。合成的βA（1-40）很容易被转谷氨酰胺酶交联，以时间依赖性方式形成多聚体。此外，还发现另一种具有与荷兰型遗传性淀粉样变性突变（Glu22变为Gln）相似取代的肽也是转谷氨酰胺酶的底物。由于转谷氨酰胺酶通过谷氨酰胺残基共价交联蛋白质，因此提示转谷氨酰胺酶在荷兰型遗传性淀粉样变性以及可能在阿尔茨海默病的淀粉样沉积中起作用。
