Neurological Disease: Are Systems Approaches the Way Forward?

Abstract

Most neurological diseases are multifactorial diseases, where environmental conditions combine with genetic background or somatic mutations to trigger a pathological state. In the case of Parkinson's Disease and Schizophrenia, recent research revealed that susceptibility genes coded for proteins involved at different steps of specific metabolic networks and cellular processes. Comprehension of the pathology of those diseases is therefore very likely to benefit from Systems approaches. This is also true of their symptomatology, affecting neurological systems at molecular, cellular, and microcircuit levels.

References

• 1 Braver TS, Barch DM, Cohen JD. Cognition and control in schizophrenia: a computational model of dopamine and prefrontal function.  Biol Psychiatry. 1999;  46 312-328
• 2 Brown JW, Bullock D, Grossberg S. How laminar frontal cortex and basal ganglia circuits interact to control planned and reactive saccades.  Neural Netw. 2004;  17 471-510
• 3 Butcher J. Neuroproteomics comes of age.  Lancet. 2007;  6 850-851
• 4 Calabresi P, Picconi B, Parnetti L, DiFilippo M. A convergent model for cognitive dysfunctions in Parkinson's disease: the critical dopamine-acetylcholine synaptic balance.  Lancet Neurol. 2006;  5 ((11)) 974-983
• 5 Calzone L, Gelay A, Zinovyev A, Radvanyi F, Barillot E. A comprehensive modular map of molecular interactions in RB/E2F pathway.  Mol Sys Biol. 2008;  , in the press
• 6 Camargo LM, Collura V, Rain JC, Mizuguchi K, Hermjakob H, Kerrien S, Bonnert TP, Whiting PJ, Brandon NJ. Disrupted in schizophrenia 1 interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia.  Mol Psych. 2007;  12 74-86
• 7 Carpenter WT, Buchanan RW. Schizophrenia.  N Engl J Med. 1994;  330 681-690
• 8 Contreras-Vidal JL, Stelmach GE. A neural model of basal ganglia-thalamocortical relations in normal and parkinsonian movement.  Biol Cybern. 1995;  73 467-476
• 9 Cookson MR. The biochemistry of Parkinson's disease.  Annu Rev Biochem. 2005;  74 29-52
• 10 Coyle JT. Glutamate and schizophrenia: beyond the dopamine hypothesis.  Cell Mol Neurobiol. 2006;  26 365-384
• 11 Cutsuridis V, Perantonis S. A neural network model of Parkinson's disease bradykinesia.  Neural Netw. 2006;  19 354-374
• 12 Exner N, Treske B, Paquet D, Holmström K, Schiesling C, Gispert S, Carballo-Carbajal I, Berg D, Hoepken HH, Gasser T, Krüger R, Winklhofer KF, Vogel F, Reichert AS, Auburger G, Kahle PJ, Schmid B, Haass C. Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin.  J Neurosci. 2007;  27 12413-12418
• 13 Fernandez E, Schiappa R, Girault JA, Le Novère N. DARPP-32 is a robust integrator of dopamine and glutamate signals.  PLoS Comput Biol. 2006;  2 e176
• 14 Garcia L, D’Alessandro G, Fernagut PO, Bioulac B, Hammond C. Impact of high-frequency stimulation parameters on the pattern of discharge of subthalamic neurons.  J Neurophysiol. 2005;  94 3662-3669
• 15 Gupta S, Bisht SS, Kukreti R, Jain S, Brahmachari SK. Boolean network analysis of a neurotransmitter signaling pathway.  J Theor Biol. 2007;  244 463-469
• 16 Han SD, Nestor PG, Shenton ME, Niznikiewicz M, Hannah G, MacCarley RW. Associative memory in chronic schizophrenia: a computational model.  Schizophr Res. 2003;  61 255-263
• 17 Humphries MD, Stewart RD, Gurney KN. A physiologically plausible model of action selection and oscillatory activity in the basal ganglia.  J Neurosci. 2006;  26 12921-12942
• 18 Kaushik P, Gorin F, Vali S. Dynamics of tyrosine hydroxylase mediated regulation of dopamine synthesis.  J Comput Neurosci. 2007;  22 147-160
• 19 Justice JB, Nicolaysen LC, Michael AC. Modeling the dopaminergic nerve terminal.  J Neurosci Methods. 1988;  22 239-252
• 20 Le Novère . The long journey to a Systems Biology of neuronal function.  BMC Systems Biology. 2007;  1 28
• 21 Limousin P, Krack P, Pollak P, Benazzouz A, Ardouin C, Hoffmann D, Benabid AL. Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease.  N Engl J Med. 1998;  339 1105-1111
• 22 Lindskog M, Kim M, Wikström MA, Blackwell KT, Kotaleski JH. Transient calcium and dopamine increase PKA activity and DARPP-32 phosphorylation.  PLoS Comput Biol. 2006;  2 e119
• 23 Mackie S, Millar JK, Porteous DJ. Role of DISC1 in neural development and schizophrenia.  Curr Opin Neurobiol. 2007;  17 95-102
• 24 Markram H. The blue brain project.  Nat Rev Neurosci. 2006;  7 153-160
• 25 Moore DJ, West AB, Dawson VL, Dawson TM. Molecular pathophysiology of Parkinson's disease.  Annu Rev Neurosci. 2005;  28 57-87
• 26 Nicholson C. Interaction between diffusion and Michaelis-Menten uptake of dopamine after iontophoresis in striatum.  Biophys J. 1995;  68 1699-1715
• 27 Patil ST, Zhang L, Martenyi F, Lowe SL, Jackson KA, Andreev BV, Avedisova AS, Bardenstein LM, Gurovich IY, Morozova MA, Mosolov SN, Neznanov NG, Reznik AM, Smulevich AB, Tochilov VA, Johnson BG, Monn JA, Schoepp DD. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial.  Nat Medecine. 2007;  13 1102-1107
• 28 Plun-Favreau H, Klupsch K, Moisoi N, Gandhi S, Kjaer S, Frith D, Harvey K, Deas E, Harvey RJ, Macdonald N, Wood NW, Martins ML, Downward J. The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1.  Nat Cell Biol. 2007;  9 1243-1252
• 29 Rao SS, Hofmann LA, Shakil A. Parkinson's disease: diagnosis and treatment.  Amer Family Phys. 2006;  74 2046-2054
• 30 Ross CA, Margolis RL, Reading SA, Pletnikov M, Coyle JT. Neurobiology of schizophrenia.  Neuron. 2006;  52 139-153
• 31 Ruppin E, Reggia JA, Horn D. Pathogenesis of schizophrenic delusions and hallucinations: a neural model.  Schizophr Bull. 1996;  22 105-123
• 32 Savitt JM, Dawson VL, Dawson TM. Diagnosis and treatment of Parkinson disease: molecules to medicine.  J Clin Invest. 2006;  116 1744-1754
• 33 Schapira AHV, Bezard E, Brotchie J, Calon F, Collingridge GL, Ferger B, Hengerer B, Hirsch E, Jenner P, Le Novère N, Obeso JA, Schwarzschild MA, Spampinato U, Davidai G. Novel pharmacological targets for the treatment of Parkinson's disease.  Nat Rev Drug Disc. 2006;  5 845-854
• 34 Setsuie R, Wada K. The functions of UCH-L1 and its relation to neurodegenerative diseases.  Neurochem Int. 2007;  51 105-111
• 35 Thanvi BR, Lo TCN. Long term motor complications of levodopa: clinical features, mechanisms, and management strategies.  Postgrad Med J. 2004;  80 452-458
• 36 Traub R, Wong RSK. Cellular mechanism of neuronal synchronisation in epilepsy.  Science. 1982;  216 745-747
• 37 Traub R, Contreras D, Cunningham M, Murray H, LeBeau F, Roopun A, Bibbig A, Wilent W, Higley M, Whittington M. Single-column thalamocortical network model exhibiting gamma oscillations, sleep spindles, and epileptogenic bursts.  J Neurophysiol. 2005;  93 2194-2232
• 38 Weihofen A, Ostaszewski B, Minami Y, Selkoe DJ. Pink1 Parkinson mutations, the Cdc37/Hsp90 chaperones and Parkin all influence the maturation or subcellular distribution of Pink1.  Hum Mol Genet. 2008;  17 602-616
• 39 Wolf JA, Moyer JT, Lazarewicz MT, Contreras D, Benoit-Marand M, O’Donnell P, Finkel LH. NMDA/AMPA ratio impacts state transitions and entrainment to oscillations in a computational model of the nucleus accumbens medium spiny projection neuron.  J Neurosci. 2005;  25 9080-9095

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