Scientific area
3.1 Basic medicine
Discipline(s)
Neurosciences (including psychophysiology)
Project title
Control of neuronal signalling pathways by CYP46A1, an enzyme involved in brain cholesterol turnover
Scientific Coordinator's name:
Elsa Rodrigues
Scientific Coordinator's e-mail:
Elsa.Rodrigues@ff.ul.pt
Principal R&D Unit:
iMed.UL/FFUL
Other R&D Units involved in the project:
-
Project keyword(s)
CYP46A1; Brain cholesterol metabolism, small GTPases, TrkB signaling
Short abstract and comments
The crucial role of cholesterol in the central nervous system physiology and cell signaling is well established, and many studies suggest that alteration in brain cholesterol homeostasis correlates with an increased risk to develop neurodegenerative diseases such as Alzheimer’s disease. The CYP46A1 gene, codes for cholesterol 24-hydroxylase, a cytochrome P450 that is specifically expressed in neurons, and is responsible for the majority of cholesterol turnover in the central nervous system. Cyp46a1 knock-out mouse exhibit severe deficiencies in spatial, associative, and motor learning, and hippocampal long-term potentiation. With this project we will contribute to the elucidation of the endogenous regulatory circuits controlled by CYP46A1 in the brain. Namely to the role these enzyme in the control of sGTPases and TrkB receptor, and its relation to neurodegenerative disorders with altered brain cholesterol metabolism, in order to understand if CYP46A1 is a suitable therapeutic target in neurodegenerative diseases associated with learning and memory impairment.
Potential uses/indications
Understand if CYP46A1 is a suitable therapeutic target in neurodegenerative diseases associated with learning and memory impairment.
Status
Ongoing
Partner Status: Seeking Partners?
No
Grant number (QREN, FP7, Eureka, etc)
FCT/PTDC/SAU-NMC/110809/2009
Last edited on
2013-11-04 13:11:38