title: The modular systems biology approach to investigate the control of apoptosis in Alzheimer's disease neurodegeneration.
abstract: Apoptosis is a programmed cell death that plays a critical role during the development of the nervous system and in many chronic neurodegenerative diseases, including Alzheimer's disease (AD). This pathology, characterized by a progressive degeneration of cholinergic function resulting in a remarkable cognitive decline, is the most common form of dementia with high social and economic impact. Current therapies of AD are only symptomatic, therefore the need to elucidate the mechanisms underlying the onset and progression of the disease is surely needed in order to develop effective pharmacological therapies. Because of its pivotal role in neuronal cell death, apoptosis has been considered one of the most appealing therapeutic targets, however, due to the complexity of the molecular mechanisms involving the various triggering events and the many signaling cascades leading to cell death, a comprehensive understanding of this process is still lacking. Modular systems biology is a very effective strategy in organizing information about complex biological processes and deriving modular and mathematical models that greatly simplify the identification of key steps of a given process. This review aims at describing the main steps underlying the strategy of modular systems biology and briefly summarizes how this approach has been successfully applied for cell cycle studies. Moreover, after giving an overview of the many molecular mechanisms underlying apoptosis in AD, we present both a modular and a molecular model of neuronal apoptosis that suggest new insights on neuroprotection for this disease.
authors.affiliation: Department of Biotechnology and Biosciences, Laboratory of Neuroscience R. Levi-Montalcini, University of Milano-Bicocca, 20126 Milan, Italy. lilia.alberghina@unimib.it
authors.forename: Lilia
authors.initials: L
authors.lastname: Alberghina
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Colangelo
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009410:Nerve Degeneration / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D009414:Nerve Growth Factors / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D049490:Systems Biology / Q000379:methods*
chemical_list: D000682:Amyloid; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D020169:Caspases