Partner 7: Academic Medical Center at the University of Amsterdam [AMC], Amsterdam,

The Netherlands

Scientist responsible: Dr. Wiep Scheper

The Academic Medical Center (AMC) is the hospital of the University of Amsterdam. In addition to being a healthcare facility and a teaching hospital, it is a major location of research related to human disease. Fundamental research of neurological diseases is situated in the Neurogenetics laboratory.
The main focus of our Alzheimer’s disease (AD) research is the involvement of protein folding and quality control in AD, in particular the stress response of the endoplasmic reticulum (ER), the unfolded protein response (UPR).  One part of our research focuses on the mechanistic aspects of Aβ toxicity, with special focus on ER stress. We use a multidisciplinary approach: from physico-chemical aspects of protein aggregates, via cellular models to the analysis of post-mortem material.

Current group members:
Wiep Scheper, PhD, PI
Line De Kimpe, PhD, post-doc
Diana Nijholt, MSc, PhD student
Hyung Elfrink, MSc, PhD student
Rob Zwart, BSc, technician

www.amc.nl/?pid=2427&rm=person&medewerkerid=222

Publications relevant to this project over the last 5 years:

E. van Someren, W. Scheper and P.J. Lucassen (2009) Neurogenesis and the unfolded protein response; new cellular and molecular avenues in sleep research. Sleep Medicine Reviews. in press.
doi:10.1016/j.smrv.2008.12.004

J.J.M. Hoozemans, E.S. van Haastert, D.A.T. Nijholt, A.J.M. Rozemuller, P. Eikelenboom and W. Scheper (2009) The Unfolded Protein Response is activated in pretangle neurons in Alzheimer’s disease hippocampus. Am. J. Pathol. in press. doi: 10.2353/ajpath.2009.080814

W. Scheper and J.J.M. Hoozemans (2009) Endoplasmic Reticulum Protein Quality Control in Neurodegenerative Disease: The Good, the Bad and the Therapy. Curr. Med. Chem.16(5):615-26.

S.M. Chafekar, R. Zwart, R. Veerhuis, H. Vanderstichele, F. Baas and W. Scheper (2008) Increased Aβ1-42 production sensitizes neuroblastoma cells for ER stress toxicity. Curr. Alzh. Res. 5: 469-574

S.M. Chafekar, F. Baas and W. Scheper (2008) Oligomer-specific A toxicity in cellmodels is mediated by selective uptake. Biochim Biophys Acta. 1782: 523-531.

E.M. Hol and W. Scheper (2008) Protein quality control in neurodegeneration: walking the tight rope between health and disease. J. Mol. Neurosci. 34: 23-33

S.M. Chafekar, H. Malda, M. Merkx, E.W. Meijer, D. Viertl,  H.A. Lashuel, F. Baas and W. Scheper (2007)  Branched KLVFF tetramers strongly potentiate inhibition of b-amyloid aggregation. ChemBiochem. 8(15): 1857-1864.

P. Eikelenboom, W.A. van Gool, J.M. Rozemuller, W. Scheper, R. Veerhuis and J.J.M. Hoozemans (2007) The involvement of Aβ in the neuroinflammatory response. In “Aβ peptide and Alzheimer’s disease” (C.J. Barlow and D.H. Small, editors), Springer Verlag, London (Ltd) ISBN-10: 1-85233-961-6/ISBN-13: 978-1-85233-961-6.

S.M. Chafekar, J.J.M. Hoozemans, R. Zwart, F. Baas and W. Scheper (2007) Aβ1-42 induces mild endoplasmic reticulum stress in an aggregation state dependent manner. Antioxid. Redox Sign. 9 (12): 2245-54

W. Scheper, J.J.M. Hoozemans, C.C. Hoogenraad, A.J.M. Rozemuller, P. Eikelenboom and F. Baas (2007) Rab6 is increased in Alzheimer’s disease brain and correlates with endoplasmic reticulum stress. Neuropathol. Appl. Neurobiol. 33(5): 523-32

J.J.M. Hoozemans, E.S. van Haastert, P. Eikelenboom, R.A.I. de Vos, J.M. Rozemuller, W. Scheper (2007) Activation of the unfolded protein response in Parkinson’s disease. Biochem. Biophys. Res. Commun. 354:707-11

Y.S. Kap, J.J.M. Hoozemans, A.J. Bodewes, R. Zwart, O.C. Meijer, F. Baas and W. Scheper (2007) Pin1 levels are downregulated during ER stress in human neuroblastoma cells. Neurogenetics 8: 21-7

J.J.M. Hoozemans, S.M. Chafekar, F. Baas, P. Eikelenboom and W. Scheper (2006) Always around, never the same: Pathways of amyloid beta induced neurodegeneration throughout the pathogenic cascade of Alzheimer’s disease. Current Medicinal Chemistry  13: 2599-2605
J.J.M. Hoozemans, J. Stieler, E.S. van Haastert, R. Veerhuis, A.J.M. Rozemuller, F. Baas, P. Eikelenboom, T. Arendt, W. Scheper (2006) The unfolded protein response affects neuronal cell cycle protein expression: Implications for Alzheimer's disease pathogenesis. Exp. Gerontology 41: 380-6

E.M. Hol, D.F. Fischer, H. Ovaa  and W. Scheper (2006) The ubiquitin proteasome system as a pharmacological target in neurodegeneration. Expert Review of Neurotherapeutics 6: 1337-47
P. Eikelenboom, R. Veerhuis, W. Scheper, A.J. Rozemuller, van Gool, W.A. and J.J.M. Hoozemans (2006) The significance of neuroinflammation in understanding Alzheimer's disease. J. Neural. Transm. 113: 1685-95.

J.J.M. Hoozemans, E.S. van Haastert, R. Veerhuis, T. Arendt, W. Scheper, P. Eikelenboom and A. Rozemuller (2005) Neuronal expression of COX-2 and phospho-pRb precedes glial activation in Alzheimer’s disease. J. Neuroinflammation 2: 27

W. Scheper and E.M. Hol (2005) Protein quality control in Alzheimer’s disease: A fatal saviour. Current Drug Targets-CNS & Neurological disorders. 4: 283-292.

J.J. Hoozemans, R. Veerhuis, A. Rozemuller, F. Baas, P. Eikelenboom, W. Scheper (2005) The unfolded protein response is activated in Alzheimer's disease. Acta Neuropathologica, 110:165-72

W. Scheper, R. Zwart and F. Baas (2004) Alternative splicing in the N-terminus of Alzheimer’s Presenilin 1. Neurogenetics. 5: 223-227