α-突触核蛋白异常沉积后的成分改变

Changes of α-synuclein After Accumulation

神经元内α-突触核蛋白(α-syn)异常沉积见于许多神经系统变性疾病中,如帕金森氏病、路易体痴呆、多系统萎缩等。溶酶体酶是清除α-syn的主要途径之一。在溶酶体酶Cathepsin D(CD)缺乏的小鼠中,已经发现有α-syn异常沉积。为了明确溶酶体出现缺陷后,体内α-syn异常沉积的过程,对野生型和CD-/-小鼠的皮层作抗α-syn抗体的Western blot,分析了CD-/-小鼠大脑皮层内α-syn的成分改变。结果发现,α-syn单体在两种小鼠大脑皮层的可溶性和不溶性成分里均没有明显变化,α-syn其他成分CD-/-小鼠则比野生型明显增多,特别是在可溶性成分里的大小位于分子量25～37kD之间,CD-/-小鼠有明显的带存在而野生型的没有。结果提示,溶酶体功能的正常对于α-syn的代谢有重要的作用,其功能的缺失主要是影响α-syn多倍体成分,推测体内正常的α-syn除了单体,也有多倍体存在。溶酶体功能的异常引起该平衡失调,导致大量的大分子量的α-syn异常出现,直至导致α-syn聚集体的出现。

Deposition of filamentous structures of α-synuclein （α- syn） in the neuronal cytoplasm is a common pathological feature of many neurological diseases, such as Parkinson＇s disease, dementia with Lewy bodies, and multiple system atrophy. Lysosome is one of the main clearance ways for α-syn degradation. The α-syn accumulation has been found in the lysosome enzyme Cathepsin D （CD） deficient mice in our previous work. However, little is known about how cells handle protein aggregates. To study the process of α-syn accumulation, the bands in the α-syn Western blot were analyzed in the soluble and insoluble homogenate of the wide type and CD knock out mice. Obvious changes were not found in the monomer α-syn, however, they were found in other bands, especially between 25-37 kD. These results suggest that lysosomalfunctions are important to the equilibrium of α-syn metabolism, especially to the oligomer. It is speculated that natural α-syn may exist in the form of monomer, as well as oligomer. The dysfuetion of lysosomal will lead to the imbalance between monomer and oligomer of α-syn untill the α-syn form accumulation.