Lysosomal Dysfunction in Down Syndrome is APP-Dependent and Mediated by APP-βCTF
- Description
Lysosomal failure plays an important role in the pathogenesis of many congenital neurodegenerative disorders, such as Alzheimer’s disease (AD) and Down syndrome (DS). This study showed that lysosomal dysfunction in DS requires the extra gene copy of amyloid precursor protein (APP) and is specifically mediated by the β cleaved carboxy terminal fragment of APP (APP-βCTF). In primary fibroblasts from individuals with DS, lysosomal degradation of autophagic and endocytic substrates is selectively impaired, which causes them to accumulate in enlarged autolysosomes/lysosomes. RNA sequencing was performed on six trisomic and six disomic human fibroblasts samples (3 replicates from 2 individuals in each group) from 5 months (3 replicates) and 2 years (3 replicates) old unrelated individuals treated with either small interfering RNA against human APP (siAPP) or a negative control dicer-substrate small interfering RNA (DsiRNA).
Access
- Restrictions
-
Free to All
- Instructions
- RNA sequencing data have been deposited in Gene Expression Omnibus (GEO).
- Grant Support