Format

Send to

Choose Destination

See 1 citation found by title matching your search:

J Neuropathol Exp Neurol. 2014 Mar;73(3):234-43. doi: 10.1097/NEN.0000000000000045.

Donepezil enhances Purkinje cell survival and alleviates motor dysfunction by inhibiting cholesterol synthesis in a murine model of Niemann Pick disease type C.

Author information

1
From the Adult Stem Cell Research Center (YS, YS, H-SK, IK, I-SH, SWC, K-RY, K-SK), and The Research Institute for Veterinary Science (K-SK), College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.

Abstract

Neurodegenerative processes are often accompanied by disruption of cholinergic systems; therefore, acetylcholinesterase (AChE) inhibitors (AChEIs) may have therapeutic potential in some neurological conditions. We evaluated the effects of administration of donepezil, a widely used AChEI, in the cerebellum in a murine model of Niemann-Pick disease type C (NPC). The NPC mice developed Purkinje cell loss at the age of 8 weeks; 4-week-old NPC mice given donepezil led to improvement of Purkinje cell survival that was associated with improvement of motor dysfunction in the mice. Because abnormal accumulation of cholesterol caused by impaired lipid homeostasis is the principal pathogenetic mechanism underlying NPC, we investigated the effects of donepezil on cholesterol metabolism in the NPC mice. Donepezil treatment reduced cholesterol accumulation in adult neural stem cells in vitro, and it downregulated the expression of the cholesterol synthesis factors' sterol regulatory element-binding proteins and 3-hydroxy-3-methylglutaryl-CoA reductase in the cerebellum, implying that AChE activity might be associated with cholesterol homeostasis. Taken together, our findings suggest the role of a cholinergic pathway as a novel regulator of NPC progression and the potential application of AChEIs for the treatment of human NPC.

PMID:
24487798
DOI:
10.1097/NEN.0000000000000045
[Indexed for MEDLINE]

Publication type, MeSH terms, Substances

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center