Sirtuin1 prevents axonal degeneration in adreno-leukodystrophy
Event details
| Date | 09.04.2014 |
| Hour | 14:00 › 15:00 |
| Speaker | Aurora Pujol, MD, PhD, Institut de Investigacio Biomedica de Bellvitge (IDIBELL), Barcelona (E) |
| Location | |
| Category | Conferences - Seminars |
SEMINAR of the LAUSANNE INTEGRATIVE METABOLISM and NUTRITION ALLIANCE (LIMNA)
Abstract:
Oxidative stress and mitochondria dysfunction are noxious factors, intertwined in the ethiological core of most common neurodegenerative conditions. In the peroxisomal disease adrenoleukodystrophy, caused by loss of function of the peroxisomal transporter of very long-chain fatty acids Abcd1, we have identified an early oxidative stress leading to late onset axonal degeneration and disability. In this study, we demonstrate that excess of the VLCFA C26:0 generates mitochondrial ROS, resulting in mitochondrial DNA and protein oxidation. This is concomitant with mitochondrial depletion in spinal cords attributable to an impairment of SIRT1/PGC-1a pathway. Treating X-ALD mice with resveratrol, a SIRT1 activator, or overexpressing SIRT1 by transgenesis, normalises mitochondria numbers and respiration, preserves energetic homeostasis including NADH and ATP levels and most importantly, halts axonal degeneration and related motor disability. These results link mitochondria malfunction to axonal damage, and underscore the Sirt1/PGC-a axis as a pivotal therapeutic target for neurodegenerative disease.
Bio:
Currently: ICREA Professor of Research, Neurometabolic Diseases Laboratory, Institut de Investigacio Biomedica de Bellvitge (IDIBELL), Hospital Duran i Reynals, L'Hospitalet de Llobregat
1993 Medical Degree from the Autonomous University of Barcelona, Spain
1998 PhD Thesis Degree the DKFZ, University Ruprechts-Karls, Heidelberg, Germany
1998-2002 Postdoctoral fellow at the IGMBC, Human Molecular Genetics Department, Strasbourg, France
2002 Consultant in Medical Genetics, Université Louis Pasteur and Hôpitaux Universitaires de, Strasbourg, France
2003-2004 Junior Group Leader at the IGBMC, Strasbourg, France
2005 ICREA Reseach Professor and Group Leader at IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
Link to Speaker's Lab website
Link to PEROXISOME database (PeroxisomeDB)
Abstract:
Oxidative stress and mitochondria dysfunction are noxious factors, intertwined in the ethiological core of most common neurodegenerative conditions. In the peroxisomal disease adrenoleukodystrophy, caused by loss of function of the peroxisomal transporter of very long-chain fatty acids Abcd1, we have identified an early oxidative stress leading to late onset axonal degeneration and disability. In this study, we demonstrate that excess of the VLCFA C26:0 generates mitochondrial ROS, resulting in mitochondrial DNA and protein oxidation. This is concomitant with mitochondrial depletion in spinal cords attributable to an impairment of SIRT1/PGC-1a pathway. Treating X-ALD mice with resveratrol, a SIRT1 activator, or overexpressing SIRT1 by transgenesis, normalises mitochondria numbers and respiration, preserves energetic homeostasis including NADH and ATP levels and most importantly, halts axonal degeneration and related motor disability. These results link mitochondria malfunction to axonal damage, and underscore the Sirt1/PGC-a axis as a pivotal therapeutic target for neurodegenerative disease.
Bio:
Currently: ICREA Professor of Research, Neurometabolic Diseases Laboratory, Institut de Investigacio Biomedica de Bellvitge (IDIBELL), Hospital Duran i Reynals, L'Hospitalet de Llobregat
1993 Medical Degree from the Autonomous University of Barcelona, Spain
1998 PhD Thesis Degree the DKFZ, University Ruprechts-Karls, Heidelberg, Germany
1998-2002 Postdoctoral fellow at the IGMBC, Human Molecular Genetics Department, Strasbourg, France
2002 Consultant in Medical Genetics, Université Louis Pasteur and Hôpitaux Universitaires de, Strasbourg, France
2003-2004 Junior Group Leader at the IGBMC, Strasbourg, France
2005 ICREA Reseach Professor and Group Leader at IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
Link to Speaker's Lab website
Link to PEROXISOME database (PeroxisomeDB)
Practical information
- Informed public
- Free
Organizer
- Kristina Schoonjans and Johan Auwerx (for the LIMNA Alliance)
Contact
- Johan Auwerx
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