Understanding the molecular mechanisms of neurodegenerative diseases using a computational approach (Contributo in atti di convegno)

Type
Label
  • Understanding the molecular mechanisms of neurodegenerative diseases using a computational approach (Contributo in atti di convegno) (literal)
Anno
  • 2011-01-01T00:00:00+01:00 (literal)
Alternative label
  • Alfieri R, Maj C, Mosca E, Milanesi L. (2011)
    Understanding the molecular mechanisms of neurodegenerative diseases using a computational approach
    in Multiscale Modeling, Basilea, CH, 23-24 giugno 2011
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Alfieri R, Maj C, Mosca E, Milanesi L. (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • CNR-ITB (literal)
Titolo
  • Understanding the molecular mechanisms of neurodegenerative diseases using a computational approach (literal)
Abstract
  • Calcium ions coordinate multiple cellular functions, among which the release of neurotransmitters, the gene expression, the regulation of inflammatory processes and the activation of apoptosis. The regulation of calcium metabolism involves several biochemical pathways, different sub-cellular compartments and it is strongly compromised during aging. In fact, alterations of the calcium signalling process are frequent in the neurodegenerative diseases and mainly result in the hyper-activation of the apoptotic process. To investigate molecular alterations occurring in neurodegenerative diseases, an integrative mathematical model designed to represent the calcium metabolism has been defined. The model, which is mathematically defined by ODEs system, reproduces the calcium ions functions during glutamate stimulation. In particular, a number of different situations, such as (i) the glutamatergic transmission using different impulse frequencies, (ii) the comparison between normal and excessive stimulation and (iii) the calcium homeostasis in young/aging neurons have been reproduced. In particular, the simulations of several features associated to neurodegenerative disease, especially at molecular level and with a particular focus on the apoptotic process, allow highlighting the differences occurring in calcium metabolism in normal and pathological states. Furthermore collecting the achieved simulation and sensitivity analysis results, we propose an in silico strategy for preventing the activation of the apoptotic pathway in the neurodegenerative diseases. (literal)
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