Eriksen Jason L, Przedborski Serge, Petrucelli Leonard
Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA.
Trends Mol Med. 2005 Mar;11(3):91-6. doi: 10.1016/j.molmed.2005.01.001.
Four recent papers related specifically to the familial form of Parkinson's disease reinforce the idea that endogenous levels of alpha-synuclein can strongly influence disease phenotype. Two recent publications of alpha-synuclein-duplication mutations show that the severity of familial Parkinsonian phenotype is dependent upon SNCA gene dosage and corresponding protein levels. Familial point mutations in SNCA were found to impair the efficient lysosomal degradation of alpha-synuclein, potentially resulting in elevated levels of alpha-synuclein. Conversely, the complete knockout of SNCA has little effect on transgenic mice. It is now clear that the regulation of alpha-synuclein levels has potential significance in the pathogenesis and treatment of sporadic PD.
最近有四篇专门针对帕金森病家族形式的论文强化了这样一种观点，即内源性α-突触核蛋白水平可强烈影响疾病表型。最近两篇关于α-突触核蛋白重复突变的出版物表明，家族性帕金森病表型的严重程度取决于SNCA基因剂量和相应的蛋白质水平。发现SNCA中的家族性点突变会损害α-突触核蛋白的有效溶酶体降解，可能导致α-突触核蛋白水平升高。相反，SNCA的完全敲除对转基因小鼠几乎没有影响。现在很清楚，α-突触核蛋白水平的调节在散发性帕金森病的发病机制和治疗中具有潜在意义。
