Selective neurodegeneration in murine mucopolysaccharidosis VII is progressive and reversible
Selective neurodegeneration in murine mucopolysaccharidosis VII is progressive and reversible
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DOI：
10.1002/ana.10373
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发表时间：
2002-12-01
影响因子：
11.2
通讯作者：
Wolfe, JH
中科院分区：
文献类型：
--
作者：
Heuer, GG;Passini, MA;Wolfe, JH
粘多糖沉积症是由参与糖胺聚糖降解途径的溶酶体酶的遗传缺陷引起的。溶酶体蓄积导致细胞和器官功能障碍，包括智力迟钝。在整个患病的大脑中发现了储存损伤，但对脑功能障碍的细胞和分子机制知之甚少。在粘多糖沉积症VII的小鼠模型中，我们发现大脑的特定区域易受神经变性的影响，其特征在于存在泛素包涵体、神经丝包涵体和反应性星形胶质细胞增生。病理改变主要发生在海马和大脑皮质，并随年龄增长而增加。用重组病毒载体治疗以纠正酶缺陷，定量地将靶区域的神经退行性病变逆转至正常水平。
The mucopolysaccharidoses are caused by inherited deficiencies of lysosomal enzymes involved in the degradative pathway of glycosaminoglycans. Lysosomal storage leads to cellular and organ dysfunction, including mental retardation. Storage lesions are found throughout the diseased brain, but little is known about the cellular and molecular mechanisms that underlie brain dysfunction. In the mouse model of mucopolysaccharidosis VII, we found that specific regions of the brain are vulnerable to neurodegeneration, characterized by the presence of ubiquitin inclusions, neurofilament inclusions, and reactive astrogliosis. The pathological lesions were found predominantly in the hippocampus and cerebral cortex, and they increased progressively with age. Treatment with a recombinant viral vector to correct the enzymatic defect quantitatively reversed the neurodegenerative lesions in targeted regions to normal levels.