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Peroxisomal impairment in Niemann-Pick type C disease
S Schedin1, P J Sindelar, P Pentchev
1Department of Biochemistry, Stockholm University, S-106 91 Stockholm, Sweden. fia@biokemi.su.se
The Journal of Biological Chemistry
|March 7, 1997
Summary
Niemann-Pick type C disease involves lysosomal dysfunction, but this study reveals early peroxisomal impairment. Peroxisomal enzyme defects precede disease onset, suggesting a key role in Niemann-Pick C development.
Area of Science:
- Biochemistry
- Cell Biology
- Genetics
Background:
- Niemann-Pick type C (NPC) is a lysosomal storage disorder.
- Characterized by cholesterol and sphingomyelin accumulation.
- Previously attributed solely to lysosomal dysfunction.
Purpose of the Study:
- Investigate cellular mechanisms in Niemann-Pick type C.
- Examine lysosomal, mitochondrial, microsomal, and peroxisomal function.
- Determine the role of peroxisomal impairment in NPC pathogenesis.
Main Methods:
- Utilized a mutant mouse model of Niemann-Pick type C.
- Assessed enzymatic markers in liver and brain tissues.
- Analyzed peroxisomal enzyme activities and phospholipid changes.
Main Results:
- Observed decreased peroxisomal beta-oxidation and catalase activity in brain and liver.
- Isolated peroxisomes showed significantly reduced enzyme activities.
- Plasmalogen levels and dimethylacetal patterns were altered in brain phospholipids.
- Peroxisomal enzyme defects were detected 18 days before disease onset, while lysosomal enzyme activity increased only 6 days post-symptom onset.
Conclusions:
- Niemann-Pick type C disease involves significant peroxisomal dysfunction.
- Peroxisomal impairment is an early event in NPC development.
- This contrasts with the previously held view of primary lysosomal deficiency.