Anders Nykjær

Neurotrophins (NT) stimulate survival and differentiation of neurons. However, their precursors (proNT) are apoptotic and induce death of neurons during specific phases of development and aging but also in disorders characterized by acute and insidious neurodegeneration. Sortilin acts as the molecular switch that enables a neuron to respond to a secreted proNT by survival of death. When sortilin is co-expressed with the p75 neurotrophin receptor (p75NTR) binding of proNT induces apoptosis (left panel). In the absence of sortilin, extracellular proteases cleave proNT to mature NT, promoting trophic stimulation via binding to a receptor complex comprising a tyrosine receptor-kinase Trk and p75NTR (right panel). The relative balance between apoptotic and trophic cues determines cell fate.

Group Leader

Anders Nykjær
Professor, MD, PhD
More information

RESEARCH
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. They engage in cellular trafficking as well as in signaling from the plasma membrane (Nature Rev Neurosci 2008, 9:899-909). For instance, studies in the lab uncovered that sortilin acts as a molecular switch that enables neurons to respond to a pro-neurotrophin by survival of death (see figure) (Nature 2004, 427:843-8; Nat Neurosci. 2007, 10:1449-57; Nat Neurosci. 2011, 14:54-61). Dysfunction of the Vps10p-domain receptors is associated with several neurological, psychiatric and metabolic disorders including Alzheimer’s diseases and other neurodegenerative conditions, schizophrenia, bipolar disorder, hypercholesterolemia and diabetes. Using a broad repertoire of molecular, cellular and genetic tools we aim at identifying the biological pathways regulated by Vps10p-domain receptors in health and disease.

RESEARCH INTERESTS
Vps10p-domain receptors in:

Neuronal survival and death

Neurite differentiation

Neurodegenerative disorders, i.e. Alzheimer’s disease and frontotemporal dementia

Synaptic plasticity and psychiatric disorders

Neurotrophin signaling in the central and peripheral nervous system

Axonal trafficking

Neuropathic pain

Type-2 diabetes and cholesterol metabolism

METHODOLOGIES

State-of-the-art biochemistry and cell biology

Development and phenotypic characterization of obligate and conditional transgenic mouse models

Primary neuronal cultures and explants

Signaling pathways, axon guidance, growth cone collapse and apoptosis induction

Two-photon microscopy and live imaging

Viral overexpression in vivo

Electrophysiology

Models of neuropathic pain 

Mouse behavior

COLLABORATORS & Centers

  • Professor Thomas E. Willnow, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
  • Professor Barbara L. Hempstead, Cornell University, New York, NY
  • Professor Moses V. Chao, NYU Medical Center, New York, NY
  • Professor Stephen Strittmatter, Yale University, New Haven, CT
  • Professor William C. Mobley, Stanford University and UCSD, CA

RESEARCH GROUP MEMBERS
Simon Glerup Pedersen, Assistant Professor, MD;  Mads Kjølby, MD; Karen Marie Pedersen, MD; Ulrik Bølcho, MD;  Anja N. Fjorback, MD; Ditte Olsen, PhD student; Mette Richner, PhD student; Benedicte Vestergaard. technician; Anja Aagaard Danneskjold Pedersen, technician

                                            

Henvendelse om denne sides indhold: 
Revideret 03.08.2016