Scientific Focus
Brain degeneration is a frequent problem at old age, but its prevention is currently impossible.
Microscopic studies have revealed quite specific patterns and hallmarks of neurodegeneration,
but hypothesis-driven biochemical and molecular research has failed to understand the underlying causes.
Many of these diseases may be inherited in a monogenic manner in exceptional families,
allowing hypothesis-free genetic approaches:
- Define the chromosomal localization and identify the mutations of the disease gene;
- Study the subcellular localization and the protein and RNA interactions of the mutant disease protein;
- Generate and characterize mouse mutants, which define the function of the disease protein
or which are engineered to model and study initial stages of the disease process.
- Survey expression changes across all genes within tissues from patients or mutant animals.
- Define biomarkers to quantify disease severity and progression,
in order to validate the benefit of preventive therapies.
Clinically, the group is focussed on
- the PARK6 versus PARK2, PARK5 versus PARK1 variants of Parkinson's Disease,
- the SCA2 versus SCA3 variants of Cerebellar Ataxia,
- the familial variants of Intracranial Aneurysms.
Methods
Our group uses a wide spectrum of techniques, including
- the analysis of tissues and (transfected) cultured cells with mutation screens, molecular biology,
transcriptome studies, immunohistochemistry and fluorescent microscopy, biochemistry of
protein interactions and of oxidative stress;
- the analysis of patients / mice with neurological motor or behaviour tests, with electrophysiological tests
or with brain imaging analysis (in cooperation with Prof. Hilker);
Selected Publications
Korsching S, Auburger G, Heumann R, Scott J, Thoenen H (1985) Levels of Nerve Growth Factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation. EMBO J, 4:1389-1393.
Orozco G, Nodarse A, Cordoves R, Auburger G (1990) Autosomal dominant cerebellar ataxia: Clinical analysis of 263 patients from a homogeneous population in Holguin, Cuba. Neurology, 40:1369-1375.
Auburger G, Orozco G, Ferreira R, Gispert S, Paradoa M, Estrada M, Garcia M, Farrall M, Williamson R, Chamberlain S, Heredero L (1990) Autosomal dominant ataxia: Genetic evidence for locus heterogeneity from a Cuban founder effect population. Am J Hum Genet, 46:1163-1177.
Gispert S, Twells R, Orozco G, Brice A, Weber J, Heredero L, Scheufler K, Riley B, Allotey R, Nothers C, Hillermann R, Lunkes A, Khati C, Stevanin G, Hernandez A, Margarińo C, Klockgether T, Durr A, Chneiweiss H, Enczmann J, Farrall M, Beckmann J, Mullan M, Wernet P, Agid Y, Freund H-J, Williamson R, Auburger G§, Chamberlain S§ (1993) Chromosomal assignment of the second (Cuban) locus for autosomal dominant cerebellar ataxia (SCA2) to human chromosome 12q23-24.1. Nat Genet, 4:295-299.
Auburger G, Ratzlaff T, Lunkes A, Nelles HW, Leube B, Binkofski F, Kugel H, Heindel W, Seitz R, Benecke R, Witte OW, Voit T (1995) A gene for autosomal dominant paroxysmal choreoathetosis/spasticity maps to the vicinity of a potassium gene cluster on chromosome 1p, probably within 2 cM between D1S443 and D1S197. Genomics, 31:90-94.
Lunkes A, Hartung U, Magarińo C, Rodríguez M, Palmero A, Rodríguez L, Heredero L, Weissenbach J, Weber J, Auburger G (1995) Refinement of the OPA1 gene locus on chromsome 3q28-q29 to a region of 2 to 8 centiMorgans in one Cuban pedigree with autosomal dominant optic atrophy type Kjer. Am J Hum Genet, 57:965.
Pulst S, Nechiporuk A, Nechiporuk T, Gispert S, Chen X, Lopes-Cendes I, Pearlman S, Starkman S, Orozco G, Lunkes A, de Jong P, Rouleau G, Auburger G, Korenberg JR, Figueroa C, Sahba S (1996) Moderate expansion of a normally biallelic trinucleotide repeat in Spinocerebellar ataxia 2. Nat Genet, 14:269-276.
Leube B, Rudnicki D, Ratzlaff T, Kessler KR, Benecke R und Auburger G (1996) Idiopathic torsion dystonia: assignment of a gene to chromosome 18p in a German family with adult onset, autosomal dominant inheritance and purely focal distribution. Hum Mol Genet, 5:1673-1677.
Hofele K, Benecke R, Auburger G (1997) The gene locus of the dystonic Mount-Reback type of autosomal dominant paroxysmal choreoathetosis. Neurology, 49:1252-1257.
Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, Harta G, Brownstein MJ, Jonnalagada S, Chernova T, Dehejia A, Lavedan C, Gasser T, Steinbach PJ, Wilkinson KD, Polymeropoulos MH (1998) A mutation in the Ubiquitin-hydrolase L1 gene in a family with Parkinson’s disease suggests a role for the ubiquitin pathway in neurodegenerative disorders. Nature, 395:451-2.
Auburger G (1998) New Genetic concepts and Stroke Prevention. Cerebrovasc Dis, 8 S5:28-32.
Estrada R, Galarraga J, Orozco G, Nodarse A, Auburger G (1999) Spinocerebellar ataxia 2 (SCA2): Morphometric analyses in 11 autopsies characterize it as an olivo-ponto-cerebellar atrophy (OPCA) plus. Acta Neuropathol, 97:306-310.
Nussbaum R, Auburger G (2000) Neurodegeneration in the polyglutamine diseases: Act1, Scene 1. Nat Neurosci, 3:103-104.
Sedelis M, Hofele K, Auburger GW, Morgan S, Huston JP, Schwarting RKW (2000) MPTP susceptibility in the mouse: behavioral, neurochemical and histological analysis of gender and strain differences. Behav Genet, 30:171-82.
Alexander C, Votruba M, Pesch UEA, Thiselton DL, Mayer S, Moore A, Rodriguez M, Kellner U, Leo-Kottler B, Auburger G, Bhattacharya SS, Wissinger B (2000) A gene encoding a dynamin-related GTPase is mutated in autosomal dominant optic atrophy (OPA1) linked to chromosome 3q28. Nat Genet, 26:211-215.
Hofer A, Hermans M, Kubassek N, Sitzer M, Funke H, Stögbauer F, Ivaskevicius V, Oldenburg J, Burtscher J, Knopp U, Schoch B, Wanke I, Hübner F, Deinsberger W, Meyer B, Boecher-Schwarz H, Poewe W, Raabe A, Steinmetz H, Auburger G (2003) Elastin Polymorphism Haplotype and Intracranial Aneurysms are not Associated in Central Europe. Stroke, 34:1207-1211.
Gispert S, Del Turco D, Garrett L, Chen A, Bernard D, Hamm-Clement J, Korf HW, Deller T, Braak H, Auburger G§, Nussbaum RL§ (2003) Transgenic mice expressing mutant A53T human alpha synuclein show neuronal dysfunction in the absence of aggregate formation. Mol Cell Neurosci, 24:419-29.
Rüb U, Del Turco D, Del Tredici K, de Vos RAI, Brunt ER, Reifenberger G, Seifried C, Schultz C, Auburger G§, Braak H§ (2003) Thalamic involvement in a spinocerebellar ataxia type 2 (SCA2) and spinocerebellar type 3 (SCA3) patient and its clinical relevance. Brain, 126:1-16.
Valente EM, Abou-Sleiman PM, Caputo V, Muquit MMK, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G§, Wood NW§ (2004) Hereditary early-onset Parkinson’s disease is caused by mutations in PINK1. Science, 304(5674):1158-60.
Velázquez-Pérez L, Seifried C, Santos-Falcón N, Abele M, Ziemann U, Almaguer LE, Martínez-Góngora E, Sánchez-Cruz G, Canales N, Pérez-González R, Velázquez-Manresa M, Viebahn B, Stuckrad-Barre S, Fetter M, Klockgether T, Auburger G (2004) Saccade velocity is controlled by polyglutamine size in Spinocerebellar ataxia type 2. Ann Neurol, 56 (3):444-7.
Lee HY, Xu Y, Huang Y, Ahn AH, Auburger GW, Pandolfo M, Kwieciski H, Grimes DA, Lang AE, Nielsen JE, Averyanov Y, Servidei S, Friedman A, van Bogaert P, Abramovic MJ, Bruno MK, Sorensen BF, Tang L, Fu YH, Ptacek LJ (2004) The gene for paroxysmal non-kinesigenic dyskinesia encodes an enzyme in a stress response pathway. Hum Mol Genet, 13 (24):3161-70.
Cabin DE, Gispert S, Murphy D, Auburger G, Myers R, Nussbaum RL (2005) Exacerbated synucleinopathy in mice expressing A53T SNCA on a Snca null background. Neurobiol Aging, 26:25-35.
Hernandez DG, Paisan-Ruiz C, McInerney-Leo A, Jain S, Meyer-Lindenberg A, Evans EW, Berman KF, Johnson J, Auburger G, Schäffer AA, Lopez G, Nussbaum RL, Singleton AB (2005) Clinical and PET evaluation of two families with Parkinson disease caused by mutation in the kinase domain of dardarin, encoded by LRRK2. Ann Neurol, 57:453-6.
Tuin I, Voss U, Kang JS, Kessler K, Nolte D, Lochmüller H, Tinschert S, Claus D, Krakow K, Pflug B, Steinmetz H, Auburger G (2006) Stages of sleep pathology in Spinocerebellar Ataxia type 2 (SCA2). Neurology, 67:1966-72.
Hoepken HH, Gispert S, Morales B, Wingerter O, Del Turco D, Mülsch A, Nussbaum RL, Muller K, Drose S, Brandt U, Deller T, Wirth B, Kudin AP, Kunz WS, Auburger G (2007) Mitochondrial dysfunction, peroxidation damage and changes in glutathione metabolism in PARK6. Neurobiol Dis, 25:401-11.
Freund HJ, Barnikol UB, Nolte D, Treuer H, Auburger G, Tass PA, Samii M, Sturm V (2007) Subthalamic-Thalamic DBS in a Case with Spinocerebellar Ataxia Type 2 and Severe Tremor a unusual clinical benefit. Mov Disord, 22, in press.
Lastres-Becker I, Rüb U, Auburger G (2007) Spinocerebellar ataxia type 2 (SCA2). Cerebellum, in press (invited review).
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