Neuroscience in Denmark


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General information

Name (center, department, group or other)
Nykjaer Group, DANDRITE, Department of Biomedicine, Aarhus University
Contact name
Anders Nykjær
Contact email
an#at#biomed#dot#au#dot#dk
Contact title
Professor, Director
Date
25. May 2016


Brief description of research activities

Research activities are focused towards the functional characterization of a family of neuronal type-1 receptors denoted Vps10p-domain receptors or sortilins. Members of this gene family, which comprises sortilin, SorCS1, SorCS2, SorCS3 and SorLA, predominate in neurons but are also present in specialized cell types outside the nervous system. The receptors are considered multifunctional as they bind a vast number of ligands including neurotrophins and their receptors, neuropeptides, Alzheimer’s precursor protein, progranulin, ApoE, and VLDL and engage in cellular trafficking and signaling dependent on the cellular context (reviewed in Trends in Neurosci 2012; Nat Rev Neurosci 2008). Using a broad repertoire of molecular, cellular and genetic tools combined with transgenic mouse models, we aim to unravel the function of the receptor family in health and disease and to evaluate the potential of the receptors as drug targets. Studies by us have demonstrated that sortilin receptors are critical regulators of neuronal survival, differentiation, functionality, and cholesterol metabolism, and that their dysfunction may cause diseases both inside and outside the nervous system (e.g. Nature 2004, Nat Neurosci 2007 and 2011, Neuron 2011 and 2014, Cell Metab 2010, and Mol. Psych 2016) Accordingly, human genetic association studies and gene targeting in mice have linked dysfunction of the receptors to schizophrenia, bipolar disorders, ADHD, Alzheimer’s Disease, fronto-temporal-lobar dementia, cardiovascular disease, and type 2 diabetes.

Competences include confocal and two-photon imaging, development of transgenic mouse and zebrafish models, neuronal culture systems, behavioral phenotyping of mice, electrophysiology, and in vivo gene transfer. Optogenetics is currently being established in the laboratory.

Keywords

Sortilins, neuronal development and signaling, trans-synaptic communication, neurodegeneration, mental disorders, animal behavior

Research tools and techniques

Transgenic mouse and zebrafish models
Two-photon imaging
Electrophysiology
Optogenetics
In vivo gene transfer

Scientific Personnel

No of Associate Professors/Postdocs: 5
No of PhD students: 3
Other: 4

Key references from within the last 5 years

Glerup S, Bolcho U, Molgaard S, Bøggild S, Vaegter CB, Smith AH, Nieto-Gonzalez JL, Ovesen PL, Fjorback AN, Kjolby M, Login H, Holm MM, Andersen OM, Nyengaard JR, Willnow TE, Jensen K, Nykjaer A. SorCS2 is required for BDNF dependent plasticity in the hippocampus. Mol Psych. 2016. Manuscript in press.

Glerup S, Olsen D, Vaegter CB, Gustafsen C, Sjoegaard SS, Hermey G, Kjolby M, Molgaard S, Ulrichsen M, Boggild S, Skeldal S, Fjorback AN, Nyengaard JR, Jacobsen J, Bender D, Bjarkam CR, Sørensen ES, Füchtbauer EM, Eichele G, Madsen P, Willnow TE, Petersen CM, Nykjaer A. SorCS2 regulates dopaminergic wiring and is processed into an apoptotic two-chain receptor in peripheral glia. Neuron. 82(5):1074-87, 2014.

Lewin GR, Nykjaer A. Pro-neurotrophins, sortilin, and nociception. Eur J Neurosci. 39(3):363-74, 2014.

Coulson EJ, Nykjaer A. Up-regulation of sortilin mediated by amyloid-β and p75(NTR): safety lies in the middle course. J Neurochem. 127(2):149-51, 2013.

Glerup S, Lume M, Olsen D, Nyengaard JR, Vaegter CB, Kjolby M, Lande AD, Bender D, Madsen P, Saarma M, Nykjaer A, Petersen CM. SorLA controls trophic stimulation of dopaminergic neurons by retrograde trafficking of GDNF/GFRα1. Cell Reports. 3(1):186-99, 2013.

Gass J, Lee WC, Cook C, Finch N, Stetler C, Jansen-West K, Lewis J, Link CD, Rademakers R, Nykjær A, Petrucelli L. Progranulin regulates neuronal outgrowth independent of Sortilin. Mol Neurodegen. 7(1):33, 2012.

Nykjaer A, Willnow TE. Sortilin: a receptor to regulate neuronal viability and function. Trends Neurosci. 35(4):261-70, 2012.

Vaegter CB, Jansen P, Fjorback AW, Glerup S, Skeldal S, Kjolby M, Richner M, Erdmann B, Nyengaard JR, Tessarollo L, Lewin GR, Willnow T, Chao MV, Nykjaer A. Sortilin associates with Trk receptors to enchance anterograde transport and neurotrophin signalling. Nat. Neurosci. 1:54-61, 2011.

Hu F, Padukkavidana T, Vægter CB, Brady OA, Zheng Y, Mackenzie IR, Feldman HH, Nykjaer A., Strittmatter SM. Sortilin-mediated endocytosis determines levels of the fronto-temporal dementia protein, progranulin. Neuron. 18;68:654-67, 2010.

Kjolby M, Andersen OM, Breiderhoff T, Fjorback AW, Pedersen KM, Madsen P, Jansen P, Heeren J, Willnow TE, Nykjaer A. Sort1, encoded by the cardiovascular risk locus 1p13.3. is a regulator of hepatic lipoprotein export. Cell Metab. 8;12:213-23, 2010.

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