Alpha-Synuclein is a presynaptic neuronal protein that is linked genetically and neuropathologically to Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Dementia with Lewy bodies (DLBs). α-Synuclein may contribute to PD and MSA pathogenesis in a number of ways. I have focused my research work on investing the role of different α-synuclein species such as monomers (isoforms, truncated variants), oligomers, fibrils, and α-synuclein post-translational modifications in these two synucleinopathies.
Moreover, a growing body of evidence from clinical studies and preclinical animal models emphasize a role of the immune system in the development of PD and MSA. I am concentrating my research on anti-α-synuclein naturally occurring autoantibodies (NAbs) as therapeutic targets and clinical biomarkers. NAbs make up two-thirds of the human antibody pool and may be involved in many functions such as regulatory and protective actions. NAbs in the central nervous system has been implicated in maintaining homeostasis by removing cell debris and are suggested to prevent inflammation by binding and neutralizing cytokines.
My research focus concentrates not only on synucleinopathies but also other proteinopathies including Alzheimer’s disease (AD) and Amyotrophic Lateral Sclerosis (ALS).
In near future we plan to expand the molecular studies from
tissue specific to cell specific by combining UV-laser microdissection- and
quantitative RT-PCR techniques with a suitable PCR assays.
Rydbirk R, Elfving B, Andersen MD, Langbøl MA, Folke J, Winge K, Pakkenberg B, Brudek T, Aznar S. Cytokine profiling in the prefrontal cortex of Parkinson's Disease and Multiple System Atrophy patients. Neurobiol Dis. 2017 Oct;106:269-278.
Brudek T, Winge K, Folke J, Christensen S, Fog K, Pakkenberg B, Pedersen LØ.
Autoimmune antibody decline in Parkinson's disease and Multiple System Atrophy; a step towards immunotherapeutic strategies. Mol Neurodegener. 2017 Jun 7;12(1):44.
Nykjaer CH, Brudek T, Salvesen L, Pakkenberg B. Changes in the cell population
in brain white matter in multiple system atrophy. Mov Disord. 2017 Apr 10.
Fomsgaard L, Moreno JL, de la Fuente Revenga M, Brudek T, Adamsen D,
Rio-Alamos C, Saunders J, Klein AB, Oliveras I, Cañete T, Blazquez G, Tobeña A,
Fernandez-Teruel A, Gonzalez-Maeso J, Aznar S. Differences in 5-HT2A and mGlu2
Receptor Expression Levels and Repressive Epigenetic Modifications at the 5-HT2A Promoter Region in the Roman Low- (RLA-I) and High- (RHA-I) Avoidance Rat
Strains. Mol Neurobiol. 2017 Mar 6.
Russ K, Flores J, Brudek T, Doudet DJ. Differential behavioral outcomes
following neonatal versus fetal human retinal pigment epithelial cell striatal
implants in parkinsonian rats. J Neural Transm (Vienna). 2017 Apr;124(4):455-462.
Rydbirk R, Folke J, Winge K, Aznar S, Pakkenberg B, Brudek T. Assessment of
brain reference genes for RT-qPCR studies in neurodegenerative diseases. Sci Rep.2016 Nov 17;6:37116.
Rasmussen NB, Olesen MV, Brudek T, Plenge P, Klein AB, Westin JE, Fog K,
Wörtwein G, Aznar S. 5-HT2A Receptor Binding in the Frontal Cortex of Parkinson's
Disease Patients and Alpha-Synuclein Overexpressing Mice: A Postmortem Study.
Parkinsons Dis. 2016;2016:3682936.
Russ K, Flores J, Brudek T, Doudet D. Neonatal Human Retinal Pigment Epithelial Cells Secrete Limited Trophic Factors in Vitro and in Vivo Following Striatal Implantation in Parkinsonian Rats. Journal of Neural Transmission, Nov 6 2015.
Brudek T, Winge K, Rasmussen NB, Bahl JM, Tanassi J, Agander TK, Hyde TM,
Pakkenberg B. Altered α-synuclein, parkin, and synphilin isoform levels in
multiple system atrophy brains. J Neurochem. 2016 Jan;136(1):172-85.
Salvesen L, Winge K, Brudek T, Agander TK, Løkkegaard A, Pakkenberg B. Neocortical Neuronal Loss in Patients with Multiple System Atrophy: A Stereological Study. Cerebral Cortex 2015 Oct 13, Epub ahead of print
Salvesen L, Ullerup BH, Sunay FB, Brudek T, Løkkegaard A, Agander TK, Winge K, Pakkenberg B. Changes in total cell numbers of the basal ganglia in patients with multiple system atrophy - A stereological study. Neurobiol Dis. Neurobiol Dis. 2015 Feb;74:104-13.
Vlassaks E, Brudek T, Pakkenberg B, Gavilanes AW. Cerebellar cytokine expression in a rat model for fetal asphyctic preconditioning and perinatal asphyxia. Cerebellum. 2014 Aug;13(4):471-8.
Møller-Larsen A, Brudek T, Petersen T, Petersen E, Aagaard M, Hansen D, Christensen T. Flow Cytometric Assay Detecting Cytotoxicity against Human Endogenous Retrovirus Antigens Expressed on Cultured Multiple Sclerosis Cells. Clin Exp Immunol. 2013 Sep;173(3):398-410.
Brudek T, Winge K, Klitmøller Agander T, Pakkenberg B. Screening of Toll-Like Receptors Expression in Multiple System Atrophy Brains Neurochem Res. 2013 Jun;38(6):1252-9.
Laska MJ, Brudek T, Nissen KK, Christensen T, Anne Møller-Larsen A, Petersen T, Nexø BA. Expression of HERV-Fc1, a human endogenous retrovirus, is increased in patients with active Multiple Sclerosis. J Virol. 2012 Apr;86(7):3713-22.
Nexø BA, Christensen T, Frederiksen J, Møller-Larsen A, Oturai AB, Villesen P, Hansen B, Nissen KK, Laska MJ, Petersen TS, Bonnesen S, Hedemand A, Wu T, Wang X, Zhang X, Brudek T, Maric R, Søndergaard HB, Sellebjerg F, Brusgaard K, Kjeldbjerg AL, Rasmussen HB, Nielsen AL, Nyegaard M, Petersen T, Børglum
AD, Pedersen FS. The etiology of multiple sclerosis: genetic evidence for the involvement of the human endogenous retrovirus HERV-Fc1. PLoS One. 2011 Feb 2;6(2):e16652.
Maric R, Pedersen FS, Kjeldbjerg A, Moeller-Larsen A, Bahrami S, Brudek T, Petersen T, Christensen T. Absence of xenotropic murine leukaemia virus-related virus in Danish patients with multiple sclerosis. J Clin Virol. 2010 Sep 7.
Brudek T, Christensen T, Petersen T, Hansen HJ, Møller-Larsen A. B cells and monocytes from patients with active multiple sclerosis exhibit increased surface expression of both HERV-H Env and HERV-W Env, accompanied by increased seroreactivity. Retrovirology 2009, 6:104.
Petersen T, Møller-Larsen A, Thiel S, Brudek T, Krarup Hansen T, Christensen T. Effects of interferon-beta therapy on innate and adaptive immune responses to human endogenous retrovirus, cytokine production, and the lectin complement activation pathway in multiple sclerosis. J Neuroimmunol. 2009 Oct 30;215(1-2):108-16.
Brudek T, Christensen T, Hansen HJ, Møller-Larsen A. Synergistic Immune Responses Induced by Endogenous Retrovirus and Herpesvirus Antigens Result in Increased Production of Inflammatory Cytokines in Multiple Sclerosis Patients. Scand.J.Imunol. 2008 Mar; 67: 295-303.
Brudek T, Luhdorf P, Christensen T, Hansen HJ, Moller-Larsen A. Activation of endogenous retrovirus reverse transcriptase in multiple sclerosis patient lymphocytes by inactivated HSV-1, HHV-6 and VZV. J Neuroimmunol 2007 Jul;187(1-2):147-55.
Christensen T, Petersen T, Thiel S, Brudek T, Ellermann-Eriksen S, Møller-Larsen A. Gene-environment interactions in multiple sclerosis: Innate and adaptive immune responses to human endogenous retrovirus and herpes virus antigens and the lectin complement activation pathway. J Neuroimmunol. 2007 Feb;183(1-2):175-88.
Brudek T, Christensen T, Hansen HJ, Bobecka J, Moller-Larsen A. Simultaneous presence of endogenous retrovirus and herpes virus antigens has profound effect on cell-mediated immune responses: implications for multiple sclerosis. AIDS Res Hum Retroviruses. 2004 Apr;20(4):415-23.