Disruption and therapeutic rescue of autophagy in a human neuronal model of Niemann Pick type C1.

ABSTRACT: An unresolved issue about many neurodegenerative diseases is why neurons are particularly sensitive to defects in ubiquitous cellular processes. One example is Niemann Pick type C1, caused by defects in cholesterol trafficking in all cells, but where neurons are preferentially damaged. Understanding this selective failure is limited by the difficulty in obtaining live human neurons from affected patients. To solve this problem, we generated neurons with decreased function of NPC1 from human embryonic stem cells and used them to test the hypothesis that defective cholesterol handling leads to enhanced pathological phenotypes in neurons. We found that human NPC1 neurons have strong spontaneous activation of autophagy, and, contrary to previous reports in patient fibroblasts, a block of autop

SUBMITTER: Ordonez MP 

PROVIDER: S-EPMC3363339 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature