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Unraveling the neuroprotective role of TUDCA in Parkinson’s disease: targeting oxidative stress and mitophagy

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)
Pharmacology and pharmacy

Project description

Project title

Unraveling the neuroprotective role of TUDCA in Parkinson’s disease: targeting oxidative stress and mitophagy

Scientific Coordinator's name:

Margarida Casal Ribeiro Castro Caldas Braga

Scientific Coordinator's e-mail:

mcastrocaldas@ff.ul.pt

Principal R&D Unit:

iMed.UL/FFUL

Other R&D Units involved in the project:

-

Project keyword(s)

Tauroursodeoxycholic acid (TUDCA); Parkinson´s disease; Oxidative stress; Mitophagy

Short abstract and comments

Mitochondrial dysfunction is deeply implicated in Parkinson’s disease (PD) progression. Thus, to impair neuronal oxidative injury it is crucial to maintain a healthy population of mitochondria. We have recently shown that tauroursodeoxycholic acid (TUDCA) protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration by still incompletely identified mechanisms. This project is the follow up of our previous work, aiming at characterizing TUDCA-induced neuroprotection in PD. One approach towards protection that has recently arisen in PD research is the selective degradation of mitochondria by mitophagy. Hence, in this project, using cellular and animal models of sporadic and familial PD, we will evaluate whether TUDCA upregulates endogenous reactive oxigen species (ROS) scavengers and increases mitochondrial turnover by mitophagy. We will also investigate the cellular pathways and mechanisms implicated in TUDCA-mitophagy. Demonstration that pharmacological upregulation of mitophagy by TUDCA delays neurodegeneration will be a huge achievement and should contribute to the validation of TUDCA application in PD.

Potential uses/indications

The overall experimental approach proposed in this project should provide new insights into the neurodegenerative process in PD as well as the neuroprotective role of TUDCA. TUDCA is an endogenous molecule, orally bioavailable, and a central nervous system penetrating agent with no associated toxicity, which is particularly important for long term use in PD. The characterization of the mechanisms through which TUDCA modulates oxidative stress and neurodegeneration should provide evidences to validate and extend its clinical application to PD.

Status

Ongoing

Partner Status: Seeking Partners?

No

Grant number (QREN, FP7, Eureka, etc)

PTDC/NEU-NMC/0248/2012

Last edited on

2013-11-04 13:46:01

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