Lab coats

Helmholtz International Research Group

Research project: Sorting receptors in control of metabolism and neurodegeneration

Disorders of the metabolism emerge as major risk factors for neurological and neurodegenerative diseases. However, the molecular mechanisms that link control of metabolism with brain function and dysfunction remain poorly understood. We identified a unique class of signaling receptors termed VPS10P domain receptors that have dual roles in regulation of neuronal viability and function in the brain (Alzheimer disease, frontotemporal lobar degeneration, bipolar disorder) and in control of glucose and lipoprotein homeostasis in metabolic tissues (type-2 diabetes, atherosclerosis, hypercholesterolemia).

To elucidate regulatory mechanisms in metabolism and brain function that converge on these VPS10P receptor pathways, I have set up a collaborative research program involving metabolism researchers of the Department of Molecular Cardiovascular Research of the MDC and neuroscientists of the MIND Center at Aarhus University (Denmark) as part of a novel Helmholtz International Research Group “Metabolism and Neurodegeneration”. I will act as coordinator of the program and principal investigator of this research group at the MDC and will closely interact with the postdoctoral fellow Dr. Mads Kjolby who acts as principal investigator at the MIND Center in Aarhus.

Together, we expect to gain important insights into the crosstalk between brain and peripheral tissues, and to elucidate disease pathways common to metabolic disturbances and dementia, the two most prevalent degenerative disorders inflicting our societies.


Publications relevant to this proposal

Vanessa Schmidt, Katharina Baum, Angelyn Lao, Katja Rateitschak, Yvonne Schmitz, Anke Teichmann, Burkhard Wiesner, Claus Munck Petersen, Anders Nykjaer, Jana Wolf, Olaf Wolkenhauer, and Thomas E Willnow (2011) Quantitative modelling of amyloidogenic processing and its influence by SORLA in Alzheimer’s disease. EMBO Journal

Mads Kjolby, Olav M. Andersen, Tilman Breiderhoff, Anja W. Fjorback, Karen Marie Pedersen, Peder Madsen, Pernille Jansen, Joerg Heeren, Thomas E. Willnow, Anders Nykjaer (2010) Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export. Cell Metab.

Willnow TE, Carlo AS, Rohe M, Schmidt V (2010) SORLA/SORL1, a neuronal sorting receptor implicated in Alzheimer´s disease. Rev Neuroscience.

V.Schmidt, A.Sporbert, M.Rohe, T.Reimer, A.Rehm, O.M.Andersen and T.E.Willnow (2007) SorLA/LR11 regulates processing of amyloid precursor protein via interaction with adaptors GGA1 and PACS1. JBC

O.M.Anderson, J.Reiche, V.Schmidt, M.Gotthardt and Thomas E. Willnow (2005). Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. PNAS.