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Control of neuronal signalling pathways by CYP46A1, an enzyme involved in brain cholesterol turnover

iMed.ULisboa/ FFULisboa Research Institute for Medicines/ Faculdade de Farmácia, Universidade de Lisboa
Project classification

Scientific area

3.1 Basic medicine

Discipline(s)

Neurosciences (including psychophysiology)

Project description

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

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