Moderne neuropsychiatrische Diagnostik

Zusammenfassung

In biologischen Systemen wird Information von DNA über mRNA zur Proteinebene weitergegeben. Durch Prozesse wie alternatives Splicen der RNA und posttranslationale Modifikationen nimmt die Komplexität von der DNA-zur Proteinebene hin zu, weshalb Genomics als alleiniger Ansatz in der neuropsychiatrischen Forschung nicht ausreichend erscheint. Der moderne Forschungsansatz Proteomics erlaubt eine massenspektrometrische Proteinidentifikation einer Vielzahl von Proben unter geringem zeitlichen Aufwand. Durch die proteomanalytische Charakterisierung von Körperflüssigkeiten (wie Blut, Liquor, Urin) können dabei Biomarker detektiert werden, die Hilfestellung bei diagnostischen Prozessen, bei der Einschätzung der individuellen Prognose und der Therapieüberwachung von psychiatrischen Erkrankungen geben können. Im Folgenden sollen aktuelle proteomanalytische Methoden und Ergebnisse zur Proteomics-Biomarker-Forschung in der Psychiatrie vorgestellt werden. Zudem werden Möglichkeiten und Limitierungen von Proteomics diskutiert.

Summary

In biosystems, information is transcribed from DNA to mRNA and finally translated at the protein level. Processes such as alternative splicing and post-translational modification increase the complexity of the translation to the mature protein. It is clear that a simple genomic approach to neuropsychiatric research is insufficient. In the modern research field of proteomics, proteins are identified usinga large-scale high-throughput mass spectrometric approach. The proteomic characterization of human biofluids is likely to result in the identification of disease biomarkers with the potential to strengthen psychiatric diagnoses, assess prognoses and monitor therapy courses. In this article we give an overview of currently used proteomic tools and discuss the results of proteomics and biomarker research in psychiatry. We will also include an assessment of the opportunities and pitfalls of proteomic technologies.

Schlüsselwörter

Proteomics - Genomics - Psychiatrie - Massenspektrometrie - Biomarker

Keywords

Proteomics - genomics - psychiatry - mass spectrometry - biomarker

• Literatur

• 1 Adkins JN, Varnum SM, Auberry KJ, Moore RJ, Angell NH, Smith RD. et al. Toward a human blood serum proteome: analysis by multidimensional separation coupled with mass spectrometry. Mol Cell Proteomics 2002; 01: 947-955.
• 2 Aebersold R, Mann M. Mass spectrometry-based proteomics. Nature 2003; 422: 198-207.
• 3 Alder J, Thakker-Varia S, Bangasser DA, Kuroiwa M, Plummer MR, Shors TJ. et al. Brain-derived neurotrophic factor-induced gene expression reveals novel actions of VGF in hippocampal synaptic plasticity. J Neurosci 2003; 23: 10800-10808.
• 4 Balgley BM, Laudeman T, Yang L, Song T, Lee CS. Comparative evaluation of tandem MS search algorithms using a target-decoy search strategy. Mol Cell Proteomics. 2007 im Druck.
• 5 Beynon RJ, Pratt JM. Metabolic labeling of proteins for proteomics. Mol Cell Proteomics 2005; 04: 857-872.
• 6 Brunner J, Bronisch T, Uhr M, Ising M, Binder E, Holsboer F. et al. Proteomic analysis of the CSF in unmedicated patients with major depressive disorder reveals alterations in suicide attempters. Eur Arch Psychiatry Clin Neurosci 2005; 255: 438-440.
• 7 Carrette O, Demalte I, Scherl A, Yalkinoglu O, Corthals G, Burkhard P. et al. A panel of cerebrospinal fluid potential biomarkers for the diagnosis of Alzheimer’s disease. Proteomics 2003; 03: 1486-1494.
• 8 Castano EM, Roher AE, Esh CL, Kokjohn TA, Beach T. Comparative proteomics of cerebrospinal fluid in neuropathologically-confirmed Alzheimer’s disease and non-demented elderly subjects. Neurol Res 2006; 28: 155-163.
• 9 Choe LH, Dutt MJ, Relkin N, Lee KH. Studies of potential cerebrospinal fluid molecular markers for Alzheimer’s disease. Electrophoresis 2002; 23: 2247-2251.
• 10 Choudhary J, Grant SG. Proteomics in postgenomic neuroscience: the end of the beginning. Nat Neurosci 2004; 07: 440-445.
• 11 Davidsson P, Westman-Brinkmalm A, Nilsson CL, Lindbjer M, Paulson L, Andreasen N. et al. Proteome analysis of cerebrospinal fluid proteins in Alzheimer patients. Neuroreport 2002; 13: 611-615.
• 12 de Noo ME, Deelder A, van der Werff M, Ozalp A, Mertens B, Tollenaar R. MALDI-TOF serum protein profiling for the detection of breast cancer. Onkologie 2006; 29: 501-506.
• 13 de Noo ME, Mertens BJ, Ozalp A, Bladergroen MR, van der Werff MP, van de Velde CJ. et al. Detection of colorectal cancer using MALDI-TOF serum protein profiling. Eur J Cancer 2006; 42: 1068-1076.
• 14 Ditzen C, Jastorff AM, Kessler MS, Bunck M, Teplytska L, Erhardt A. et al. Protein biomarkers in a mouse model of extremes in trait anxiety. Mol Cell Proteomics 2006; 05: 1914-1920.
• 15 Domon B, Aebersold R. Mass spectrometry and protein analysis. Science 2006; 312: 212-217.
• 16 Elias JE, Haas W, Faherty BK, Gygi SP. Comparative evaluation of mass spectrometry platforms used in large-scale proteomics investigations. Nat Methods 2005; 02: 667-675.
• 17 Fountoulakis M, Kossida S. Proteomics-driven progress in neurodegeneration research. Electrophoresis 2006; 27: 1556-1573.
• 18 Freeman WM, Hemby SE. Proteomics for protein expression profiling in neuroscience. Neurochem Res 2004; 29: 1065-1081.
• 19 Grant SG, Husi H. Proteomics of multiprotein complexes: answering fundamental questions in neuroscience. Trends Biotechnol 2001; 19: 49-54.
• 20 Gygi SP, Rochon Y, Franza BR, Aebersold R. Correlation between protein and mRNA abundance in yeast. Mol Cell Biol 1999; 19: 1720-1730.
• 21 Hamacher M, Meyer HE. HUPO Brain Proteome Project: aims and needs in proteomics. Expert Rev Proteomics 2005; 02: 1-3.
• 22 Huang JT, Leweke FM, Oxley D, Wang L, Harris N, Koethe D. et al. Disease biomarkers in cerebrospinal fluid of patients with first-onset psychosis. PLoS Med 2006; 03: e428.
• 23 Hye A, Lynham S, Thambisetty M, Causevic M, Campbell J, Byers HL. et al. Proteome-based plasma biomarkers for Alzheimer’s disease. Brain 2006; 129: 3042-3050.
• 24 Jiang L, Lindpaintner K, Li HF, Gu NF, Langen H, He L. et al. Proteomic analysis of the cerebrospinal fluid of patients with schizophrenia. Amino Acids 2003; 25: 49-57.
• 25 Kapp EA, Schutz F, Connolly LM, Chakel JA, Meza JE, Miller CA. et al. An evaluation, comparison, and accurate benchmarking of several publicly available MS/MS search algorithms: sensitivity and specificity analysis. Proteomics 2005; 05: 3475-3490.
• 26 Kim SI, Voshol H, van Oostrum J, Hastings TG, Cascio M, Glucksman MJ. Neuroproteomics: expression profiling of the brain’s proteomes in health and disease. Neurochem Res 2004; 29: 1317-1331.
• 27 Kromer SA, Kessler MS, Milfay D, Birg IN, Bunck M, Czibere L. et al. Identification of glyoxalase-I asa protein marker in a mouse model of extremes in trait anxiety. J Neurosci 2005; 25: 4375-4384.
• 28 La YJ, Wan CL, Zhu H, Yang YF, Chen YS, Pan YX. et al. Decreased levels of apolipoprotein A-I in plasma of schizophrenic patients. J Neural Transm 2007; 114: 657-663.
• 29 Leitner A, Lindner W. Chemistry meets proteomics: the use of chemical tagging reactions for MS-based proteomics. Proteomics 2006; 06: 5418-5434.
• 30 Lewczuk P, Esselmann H, Groemer TW, Bibl M, Maler JM, Steinacker P. et al. Amyloid beta peptides in cerebrospinal fluid as profiled with surface enhanced laser desorption/ionization time-offlight mass spectrometry: evidence of novel biomarkers in Alzheimer’s disease. Biol Psychiatry 2004; 55: 524-530.
• 31 Lewczuk P, Esselmann H, Meyer M, Wollscheid V, Neumann M, Otto M. et al. The amyloid-beta (Abeta) peptide pattern in cerebrospinal fluid in Alzheimer’s disease: evidence ofa novel carboxyterminally elongated Abeta peptide. Rapid Commun Mass Spectrom 2003; 17: 1291-1296.
• 32 Liu HC, Hu CJ, Chang JG, Sung SM, Lee LS, Yuan RY. et al. Proteomic identification of lower apolipoprotein A-I in Alzheimer’s disease. Dement Geriatr Cogn Disord 2006; 21: 155-161.
• 33 Lopez MF, Mikulskis A, Kuzdzal S, Bennett DA, Kelly J, Golenko E. et al. High-resolution serum proteomic profiling of Alzheimer disease samples reveals disease-specific, carrier-protein-bound mass signatures. Clin Chem 2005; 51: 1946-1954.
• 34 Maddalena AS, Papassotiropoulos A, Gonzalez-Agosti C, Signorell A, Hegi T, Pasch T. et al. Cerebrospinal fluid profile of amyloid beta peptides in patients with Alzheimer’s disease determined by protein biochip technology. Neurodegener Dis 2004; 01: 231-235.
• 35 Marcotte ER, Srivastava LK, Quirion R. cDNA microarray and proteomic approaches in the study of brain diseases: focus on schizophrenia and Alzheimer’s disease. Pharmacol Ther 2003; 100: 63-74.
• 36 Morris CM, Wilson KE. High throughput approaches in neuroscience. Int J Dev Neurosci 2004; 22: 515-522.
• 37 Newton RP, Brenton AG, Smith CJ, Dudley E. Plant proteome analysis by mass spectrometry: principles, problems, pitfalls and recent developments. Phytochemistry 2004; 65: 1449-1485.
• 38 Nomura F, Tomonaga T, Sogawa K, Ohashi T, Nezu M, Sunaga M. et al. Identification of novel and downregulated biomarkers for alcoholism by surface enhanced laser desorption/ionization-mass spectrometry. Proteomics 2004; 04: 1187-1194.
• 39 Poon TC. Opportunities and limitations of SELDI-TOF-MS in biomedical research: practical advices. Expert Rev Proteomics 2007; 04: 51-65.
• 40 Puchades M, Hansson SF, Nilsson CL, Andreasen N, Blennow K, Davidsson P. Proteomic studies of potential cerebrospinal fluid protein markers for Alzheimer’s disease. Brain Res Mol Brain Res 2003; 118: 140-146.
• 41 Simonsen AH, McGuire J, Hansson O, Zetterberg H, Podust VN, Davies HA. et al. Novel panel of cerebrospinal fluid biomarkers for the prediction of progression to Alzheimer dementia in patients with mild cognitive impairment. Arch Neurol 2007; 64: 366-370.
• 42 Simonsen AH, McGuire J, Podust VN, Davies H, Minthon L, Skoog I. et al. Identification of a novel panel of cerebrospinal fluid biomarkers for Alzheimer’s disease. Neurobiol Aging. 2007 im Druck.
• 43 Simonsen AH, Hansson SF, Ruetschi U, McGuire J, Podust VN, Davies HA. et al. Amyloid beta1–40 quantification in CSF: comparison between chromatographic and immunochemical methods. Dement Geriatr Cogn Disord 2007; 23: 246-250.
• 44 Sogawa K, Itoga S, Tomonaga T, Nomura F. Diagnostic values of surface-enhanced laser desorption/ionization technology for screening of habitual drinkers. Alcohol Clin Exp Res 2007; 31: 22-26.
• 45 Sullivan PF, Fan C, Perou CM. Evaluating the comparability of gene expression in blood and brain. Am J Med Genet B Neuropsychiatr Genet 2006; 141: 261-268.
• 46 Tirumalai RS, Chan KC, Prieto DA, Issaq HJ, Conrads TP, Veenstra TD. Characterization of the low molecular weight human serum proteome. Mol Cell Proteomics 2003; 02: 1096-1103.
• 47 Vercauteren FG, Bergeron JJ, Vandesande F, Arckens L, Quirion R. Proteomic approaches in brain research and neuropharmacology. Eur J Pharmacol 2004; 500: 385-398.
• 48 Wan C, Yang Y, Li H, La Y, Zhu H, Jiang L. et al. Dysregulation of retinoid transporters expression in body fluids of schizophrenia patients. J Proteome Res 2006; 05: 3213-3216.
• 49 Wan C, La Y, Zhu H, Yang Y, Jiang L, Chen Y. et al. Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene. Amino Acids 2007; 32: 101-108.
• 50 Wisor JP, Takahashi JS. Regulation of the vgf gene in the golden hamster suprachiasmatic nucleus by light and by the circadian clock. J Comp Neurol 1997; 378: 229-238.
• 51 Yang Y, Wan C, Li H, Zhu H, La Y, Xi Z. et al. Altered levels of acute phase proteins in the plasma of patients with schizophrenia. Anal Chem 2006; 78: 3571-3576.
• 52 Zhang J, Goodlett DR, Montine TJ. Proteomic biomarker discovery in cerebrospinal fluid for neurodegenerative diseases. J Alzheimers Dis 2005; 08: 377-386.
• 53 Zhang J, Goodlett DR, Quinn JF, Peskind E, Kaye JA, Zhou Y. et al. Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer disease. J Alzheimers Dis 2005; 07: 125-133. discussion 73–80.