Angel Cedazo Minguez
I work at KI 20% and my research is focused on understanding the molecular mechanism behind risk factor for neurodegenerative disorders. I am leading a research group of 6 people, including 2 assistant professors, 2 postdocs and 2 PhD students. So far, I have directed 10 PhD thesis.
From 2017, I am the Head of Neurogeneration Research at Sanofi and I am located in Paris (France)
From 2017- Professor in Molecular Neurogeriatrics, KI
From 2017- Head of Neurodegeenration Research, Sanofi
From 2006- 2017 Deputy Head of KI-Alzheimer disease research center / Neurogeriatrics
From 2014- 2017 Codirector of Swedish Brain Power. A national network of centers of excellence in Neurodegenerative disorders.
From 2014- 2017 Vice-Head of the department of neurobiology, care sciences and society
Over the years, genetic and epidemiological studies have reported gene or environmental factors that increase the risk for Alzheimer's Disease (AD), suggesting that it is a disease of multifactorial origin. We aim to contribute to understand the effects of risk factors for AD, and to define to which extent these factors are secondary actors or driving forces for cognitive decline.
Apolipoprotein E, hypercholesterolemia and AD
ApoE is the main cholesterol transporter and the presence of the E4 isoform is the major risk factor for AD. High cholesterol levels in blood is another risk factor. Our hypothesis is that ApoE4 acts in synergy with environmental factors (like hypercholesterolemia) to affect signaling pathways involved in neurodegeneration. We use several in vivo and in vitro models to explore this hypothesis.
Functions of oxysterols in brain
The metabolism of cholesterol results in the production of several oxysterols, of which the peripherally-produced 27OHC and the brain-produced 24S-OH have been suggested to play a role in AD pathogenesis. However very little is known about the biological role of these oxysterols, with the exception of its affinity for LXR receptors. We have discovered new functions of 24S-OH and 27OHC in brain, related with memory consolidation and vascular regulation. Our findings suggest that these molecules are much more than subproducts of the cellular metabolism, and can be regarded as signalling molecules of importance for normal brain function as well as for neurodegeneration.
Thioredoxin and AD
Oxidative stress (OS) is one of the pathological events occurring in AD. Thioredoxin-1 (TRX1) modulate the redox homeostasis and inhibit the apoptosis signal-regulating kinase (ASK1). We reported that the TRX1 levels is impaired in AD. We showed that Abeta neurotoxicity is mediated by TRX1 oxidations and ASK1 activation. Recently, we have described the presence of a truncated form of TRX1 (TRX80) in the brain. TRX80 is dramatically reduced in AD. Also we found that TRX80 as a protective role on Amyloid-beta neurotoxicity and aggregation. So, far TRX80 is the only endogenous anti-Amyloid beta aggregant peptide described.
Ten Selected Publications in the last 10 years
Merino-Serrais P, Loera-Valencia R, Rodriguez-Rodriguez P, Parrado-Fernandez C, Ismail MA, Maioli S, Matute E, Jimenez-Mateos EM, Björkhem I, DeFelipe J, Cedazo-MinguezA. 27-Hydroxycholesterol Induces Aberrant Morphology and Synaptic Dysfunction in Hippocampal Neurons.Cereb Cortex. 2018 Nov 3. doi: 10.1093/cercor/bhy274.
Rodriguez-Rodriguez P, Sandebring-Matton A, Merino-Serrais P, Parrado-Fernandez C, Rabano A, Winblad B, Ávila J, Ferrer I, Cedazo-Minguez A. Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons. Brain. 2017 Dec 1;140(12):3269-3285.
Bengt Winblad et al. DEFEATING ALZHEIMER'S DISEASE AND OTHER DEMENTIAS: A PRIORITY FOR EUROPEAN SCIENCE AND SOCIETY. The Lancet Neurology. 2016. Volume 15, No. 5, p455–532.
Maioli S, Lodeiro M, Merino-Serrais P, Falahati F, Khan W, Puerta E, Codita A, Rimondini R, Ramirez MJ , Simmons A, Gil-Bea FJ, Westman E, Cedazo-Minguez A. ALTERATIONS IN BRAIN LEPTIN SIGNALLING IN SPITE OF UNCHANGED CSF LEPTIN LEVELS IN ALZHEIMER’S DISEASE. Aging Cell 2015 Feb;14(1):122-9
Gil-Bea F, Akterin S, Persson T, Mateos L, Sandebring A, Avila-Cariño J, Gutierrez-Rodriguez A, Sundström E, Holmgren A, Winblad B, Cedazo-Minguez A. THIOREDOXIN-80 IS A PRODUCT OF ALPHA-SECRETASE CLEAVAGE THAT INHIBITS AMYLOID-BETA AGGREGATION AND IS DECREASED IN ALZHEIMER'S DISEASE BRAIN. EMBO Mol Med. (2012) Oct;4(10):1097-111. / Faculty of 1000
Ibañez C, Simó C, Martin-Alvarez PJ, Kivipelto M, Winblad B, Cedazo-Minguez A, Cifuentes A.TOWARDS A PREDICTIVE MODEL OF ALZHEIMER'S DISEASE PROGRESSION USING CAPILLARY ELECTROPHORESIS-MASS SPECTROMETRY METABOLOMICS. Anal Chem. (2012) Oct 16;84(20):8532-40.
L.Zheng, A. Terman, M. Hallbeck, N. Dehvari, K. Kågadal, RF Cowburn, E. Benedikz. A.Cedazo-Minguez, OXIDANT INDUCED APOPTOSIS OF CULTURED NEUROBLASTOMA CELLS IS MEDIATED BY AUTOPHAGY OF AMYLOID b-PROTEIN. Autophagy (2011) 7(12).
L.Mateos, MAM Ismail, FJ. Gil-Bea, R. Schüle, L. Schöls, R. Folkesson, I. Björkhem and A. Cedazo-Mínguez. SIDE-CHAIN OXIDIZED OXYSTEROLS REGULATE THE BRAIN RENIN-ANGIOTENSIN SYSTEM THROUGH A LIVER X RECEPTOR DEPENDENT MECHANISM. J. Biol Chem. (2011) Jul 22;286(29):25574-85.
K.J. Thomas, M. McCoy, J. Blackinton, A. Beilina, M. van der Brug, A. Sandebring, D. Miller, D. Maric, A. Cedazo-Minguez, M R Cookson. DJ-1 ACTS IN PARALLEL TO THE PINK1/PARKIN PATHWAY TO CONTROL MITOCHONDRIAL FUNCTION AND AUTOPHAGY. Hum Mol Genet. 2011 Jan 1;20(1):40-50.
L Mateos, S Akterin, F Gil‐Bea, S Spulber, A Rahman, I Björkhem, M Schultzberg, A Flores-Morales, and A. Cedazo-Mínguez. ACTIVITY-REGULATED CYTOSKELETON-ASSOCIATED PROTEIN IN RODENT BRAIN IS DOWN-REGULATED BY HIGH FAT DIET IN VIVO AND BY 27-HYDROXYCHOLESTEROL IN VITRO. Brain Pathology (2009) Jan;19(1):69-80.
2017 Professor. Karolinska Institutet
2011 Senior University Lecturer. Karolinska Institutet.
2010 Associate Professor. Karolinska Institutet.
2010 Course for future academic leaders (MAL). Karolinska Institutet.
2002 Ph.D. in medicine (Neuroscience). Karolinska Institutet. Thesis: Apolipoprotein E and Alzheimer's disease: Signals and effects
Academic honours, awards and prizes
2013. Deputy Head (prefekt) of the Department of Neurobiology, Care Sciences and Society (NVS) at KI.
2009-2012. Vice-Head of the Department of Neurobiology, Care Sciences and Society at KI
2009- present. Member of the Committee for Research and Education at the Geriatric Department of the Swedish Medical Research Council (FoU råd)
2006, 2007 and 2008. Erik Rönnbergs award for research in geriatric medicine from the Bank of Sweden Tercentenary Foundation
2003 and 2004. Hjärnfonden postdoc (Swedish Brain Foundation)
2003. Svenska Lundbeck stiftelsen.