Selective neurodegeneration in murine mucopolysaccharidosis VII is progressive and reversible.

Abstract:

: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.

journal_name

Ann Neurol

journal_title

Annals of neurology

authors

Heuer GG,Passini MA,Jiang K,Parente MK,Lee VM,Trojanowski JQ,Wolfe JH

doi

10.1002/ana.10373

keywords:

subject

Has Abstract

pub_date

2002-12-01 00:00:00

pages

762-70

issue

6

eissn

0364-5134

issn

1531-8249

journal_volume

52

pub_type

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