Proteomics—Application to the Brain

Marcus, Katrin; Schmidt, Oliver; Schaefer, Heike; Hamacher, Michael; Hall, André van; Meyer, Helmut E.

doi:10.1016/s0074-7742(04)61011-7

Cited by 25 publications

(11 citation statements)

References 69 publications

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“…Proteomic analyses are now considered invaluable tools in studies attempting to elucidate the cellular and molecular underpinnings of complex biological systems (94). As such, these approaches promise to revolutionize our understanding of the effects of pharmacological agents including drugs of abuse on the brain.…”

Section: Proteomics Analysis Of Methamphetaminementioning

confidence: 99%

Methamphetamine- and Trauma-Induced Brain Injuries: Comparative Cellular and Molecular Neurobiological Substrates

Gold

Kobeissy

Wang

et al. 2009

Biological Psychiatry

106

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The use of methamphetamine (METH) is a growing public health problem because its abuse is associated with long-term biochemical and structural effects on the human brain. Neurodegeneration is often observed in humans as a result of mechanical injuries (e.g. traumatic brain injury, TBI) and ischemic damage (strokes). In this review, we discuss recent findings documenting the fact that the psychostimulant drug, METH, can cause neuronal damage in several brain regions. The accumulated evidence from our laboratories and those of other investigators indicates that acute administration of METH leads to activation of calpain and caspase proteolytic systems. These systems are also involved in causing neuronal damage secondary to traumatic and ischemic brain injuries. Protease activation is accompanied by proteolysis of endogenous neuronal structural proteins (αII-spectrin and MAP-tau protein) evidenced by the appearance of their breakdown products after these injuries. When taken together, these observations suggest that METH exposure, like TBI, can cause substantial damage to the brain by causing both apoptotic and necrotic cell death in the brains of METH addicts who use large doses of the drug during their lifetimes. Finally, because METH abuse is accompanied by functional and structural changes in the brain similar to those in TBI, METH addicts might experience greater benefit if their treatment involved greater emphasis on rehabilitation in conjunction with the use of potential neuroprotective pharmacological agents such as calpain and caspase inhibitors similar to those used in TBI.

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Section: Proteomics Analysis Of Methamphetaminementioning

confidence: 99%

Methamphetamine- and Trauma-Induced Brain Injuries: Comparative Cellular and Molecular Neurobiological Substrates

Gold

Kobeissy

Wang

et al. 2009

Biological Psychiatry

106

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“…Proteomic analysis can provide expression profiles of proteins and their post-translational modifications in cells, tissues, and organs [7, 8]. Using proteomic approaches, Lee et al .…”

Section: Introductionmentioning

confidence: 99%

Proteome of synaptosome‐associated proteins in spinal cord dorsal horn after peripheral nerve injury

Singh

Yaster

et al. 2009

Proteomics

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Peripheral nerve injury may lead to neuroadaptive changes of cellular signals in spinal cord that are thought to contribute to central mechanisms underlying neuropathic pain. Here we used a two-dimensional electrophoresis (2-DE)-based proteomic technique to determine the global expression changes of synaptosome-associated proteins in spinal cord dorsal horn after unilateral fifth spinal nerve injury (SNI). The fifth lumbar dorsal horns ipsilateral to SNI or sham surgery were harvested on day 14 post-surgery, and the total soluble and synaptosomal fractions were isolated. The proteins derived from the synaptosomal fraction were resolved by 2-DE. We identified 27 proteins that displayed different expression levels after SNI, including proteins involved in transmission and modulation of noxious information, cellular metabolism, membrane receptor trafficking, oxidative stress, apoptosis, and degeneration. Six of the 27 proteins were chosen randomly and further validated in the synaptosomal fraction by Western blot analysis. Unexpectedly, Western blot analysis showed that only one protein in the total soluble fraction exhibited a significant expression change after SNI. The data indicate that peripheral nerve injury changes not only protein expression but also protein subcellular distribution in dorsal horn cells. These changes might participate in the central mechanism that underlies the maintenance of neuropathic pain.

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“…A number of studies have been previously performed to describe the protein expression profiles of the different components of a human brain [36,37]. Langen et al utilized a combination of 2D gel electrophoresis and MALDI mass spectrometry analysis to characterize normal human CNS and identified approximately 180 parietal cortex proteins [38].…”

Section: Discussionmentioning

confidence: 99%