Selective neurodegeneration in murine mucopolysaccharidosis VII is progressive and reversible

被引:37
作者
Heuer, GG
Passini, MA
Jiang, KL
Parente, MK
Lee, VMY
Trojanowski, JQ
Wolfe, JH
机构
[1] Childrens Hosp Philadelphia, Joseph Stokes Jr Res Inst, Div Neurol, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Vet Med, Ctr Comparat Med Genet, Philadelphia, PA 19104 USA
[4] Univ Penn, Sch Vet Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
关键词
D O I
10.1002/ana.10373
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
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收藏
页码:762 / 770
页数:9
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