Spectral properties and mechanisms that underlie autofluorescent accumulations in Batten disease.
Spectral properties and mechanisms that underlie autofluorescent accumulations in Batten disease.
复制标题
巴顿病中自发荧光积累的光谱特性和机制。
DOI：
10.1016/j.bbrc.2009.02.099
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发表时间：
2009
影响因子：
3.1
通讯作者：
Pearce,DavidA
中科院分区：
文献类型：
--
作者：
Seehafer,SabrinaS;Pearce,DavidA
神经元蜡样脂褐质病（NCL）的发病率为1/12，500活产。这些破坏性的神经退行性溶酶体贮积病的特征在于类似于在老化细胞中所见的自体荧光储存物质（AFSM）的溶酶体积累。使用来自三个遗传上不同的NCL的患者来源的淋巴母细胞，我们报告AFSM为每个NCL具有不同的光谱特性。此外，通过使用药理学抑制剂来破坏正常对照淋巴母细胞中的各种生化途径，我们已经确定微管组装和非肌肉肌球蛋白II功能的破坏导致溶酶体AFSM的积累。有趣的是，自噬的抑制不会导致AFSM。我们的结论是，除了受损的功能，这个细胞器的溶酶体外的细胞干扰可以导致在NCL中的溶酶体AFSM的积累，并可能作为细胞老化的结果。
Neuronal Ceroid Lipofuscinoses (NCLs) have an incidence of 1 in 12,500 live births. These devastating neurodegenerative lysosomal storage diseases are characterized by the lysosomal accumulation of autofluorescent storage material (AFSM) similar to that seen in aging cells. Using patient derived lymphoblasts from three genetically distinct NCLs we report that AFSM for each NCL has distinct spectral properties. Moreover, by using pharmacological inhibitors to disrupt various biochemical pathways in normal control lymphoblasts we have determined that disruptions in microtubule assembly and non-muscle myosin II function results in accumulation of lysosomal AFSM. Interestingly, inhibition of autophagy did not result in AFSM. We conclude that cellular disturbances outside the lysosome in addition to compromised function of this organelle can result in accumulation of lysosomal AFSM in NCLs and possibly as a result of cellular aging.