Anti-inflammatory Therapy With Simvastatin Improves Neuroinflammation and CNS Function in a Mouse Model of Metachromatic Leukodystrophy.

ABSTRACT: Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a functional deficiency of the lysosomal enzyme arylsulfatase A. The prevailing late-infantile variant of MLD is characterized by widespread and progressive demyelination of the central nervous system (CNS) causing death during childhood. In order to gain insight into the pathomechanism of the disease and to identify novel therapeutic targets, we analyzed neuroinflammation in two mouse models reproducing a mild, nondemyelinating, and a more severe, demyelinating, variant of MLD, respectively. Microgliosis and upregulation of cytokine/chemokine levels were clearly more pronounced in the demyelinating model. The analysis of the temporal cytokine/chemokine profiles revealed that the onset of demyelination is preceded

SUBMITTER: Stein A 

PROVIDER: S-EPMC4817791 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature