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Systems Biology in the study of Neurological Disorders: Focus on Alzheimer’s Disease

Pasinetti, Giulio M.; Hiller-Sturmhöfel, Susanne
Fonte: National Institute on Alcohol Abuse and Alcoholism Publicador: National Institute on Alcohol Abuse and Alcoholism
Tipo: Artigo de Revista Científica
Publicado em //2008 EN
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Systems biology approaches may be useful for studying the mechanisms underlying alcohol’s harmful effects on the brain. Such approaches already are used in the study of Alzheimer’s disease (AD), a progressive neurodegenerative disorder that, with the overall increase in life expectancy, will affect an increasing proportion of the population and become an increasingly serious public health concern. Systems biology approaches such as complementary DNA (cDNA) microarray analyses have helped identify several genes whose expression is altered in patients exhibiting the earliest stages of AD. Several of these genes are involved in the release of messenger molecules from the ends of nerve cells (i.e., in synaptic vesicle functioning), and their particular role in AD must be investigated further using conventional molecular biological approaches. Similarly, protein array analyses have identified candidate proteins that may play a role in the development of AD. Finally, proteomic approaches, such as certain mass spectrometry techniques, have been used to search for biomarkers of the progression from normal cognitive functioning to mild cognitive impairment and AD, which eventually may allow early and reliable diagnosis of the disease. These approaches already have yielded some candidate molecules whose validity and reliability as biomarkers of AD...

A Systems-Based Computational Model of Alcohol’s Toxic Effects on Brain Development

Gohlke, Julia M.; Hiller-Sturmhöfel, Susanne; Faustman, Elaine M.
Fonte: National Institute on Alcohol Abuse and Alcoholism Publicador: National Institute on Alcohol Abuse and Alcoholism
Tipo: Artigo de Revista Científica
Publicado em //2008 EN
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1046.4185%
Important stages during neurodevelopment include the generation of new nerve cells (i.e., neurogenesis), differentiation and migration of these cells to their final location in the brain, formation of connections with neighboring cells (i.e., synaptogenesis), and cell death of neurons that fail to form the appropriate connections. Research found that alcohol exposure during fetal development can interfere with all of these processes. A systems biology approach using computational models of brain development in different species has been used to determine the relative contributions of alcohol-induced impairment of neurogenesis and synaptogenesis to alcohol-related neurodevelopmental deficits in mice, rats, rhesus monkeys, and humans. The results obtained with these models suggest that alcohol’s impact on cell division during neurogenesis results in greater deficits in neuron numbers in the adult than the alcohol-induced increase in cell death during synaptogenesis. In primates, the accelerated development of susceptible brain regions may convey increased sensitivity to alcohol-induced neurodevelopmental deficits. Systems-based approaches, such as the computational models described here, can help to translate research findings obtained at a molecular or cellular level in different species into assessment of risk associated with alcohol exposure during human development.

Alcoholic Lung Disease

Kershaw, Corey D.; Guidot, David M.
Fonte: National Institute on Alcohol Abuse and Alcoholism Publicador: National Institute on Alcohol Abuse and Alcoholism
Tipo: Artigo de Revista Científica
Publicado em //2008 EN
Relevância na Pesquisa
930.429%
In addition to its well-known association with lung infection (i.e., pneumonia), alcohol abuse now is recognized as an independent factor that increases by three- to four-fold the incidence of the acute respiratory distress syndrome, a severe form of acute lung injury with a mortality rate of 40 to 50 percent. This translates to tens of thousands of excess deaths in the United States each year from alcohol-mediated lung injury, which is comparable to scarring of the liver (i.e., cirrhosis) in terms of alcohol-related mortality. Experimental and clinical studies are shedding light on the basic mechanisms by which alcohol abuse predisposes some people to both acute lung injury and pneumonia. At the same time, novel therapeutic targets could be utilized in treating these uniquely vulnerable people. However, there have been no systems biological approaches to the study of the alcoholic lung to date. This is in part because the association between alcohol abuse and acute lung injury was made relatively recently and remains largely unrecognized, even by lung researchers. In parallel, efforts to study complex diseases such as acute lung injury and pneumonia using a genomics and/or proteomics approach, which involves the study of an organism’s genes and/or proteins...