Proteomic Analysis in the Neurosciences

Morrison, Richard S.; Kinoshita, Yoshito; Johnson, Mark D.; Uo, Takuma; Ho, Joseph T.; McBee, Joshua K.; Conrads, Thomas P.; Veenstra, Timothy D.

doi:10.1074/mcp.r200004-mcp200

Cited by 63 publications

(45 citation statements)

References 57 publications

(46 reference statements)

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“…PTMs are important processes that are able to affect directly protein function, stability, conformation, binding interactions, and localization, all of which may be important to the events that also occur after SCI (32,33). Our 2D PAGE results indicated that protein spots 46 and 49 were both Hsp27 (Fig.…”

Section: Confirmation Of the Differential Expression Of The Protein Gmentioning

confidence: 75%

Involvement of Acidic Fibroblast Growth Factor in Spinal Cord Injury Repair Processes Revealed by a Proteomics Approach

Tsai¹,

Shen²,

Kuo

et al. 2008

Molecular & Cellular Proteomics

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Acidic fibroblast growth factor (aFGF; also known as FGF-1) is a potent neurotrophic factor that affects neuronal survival in the injured spinal cord. However, the pathological changes that occur with spinal cord injury (SCI) and the attribution to aFGF of a neuroprotective effect during SCI are still elusive. In this study, we demonstrated that rat SCI, when treated with aFGF, showed significant functional recovery as indicated by the Basso, Beattie, and Bresnahan locomotor rating scale and the combined behavior score (p < 0.01-0.001). Furthermore proteomics and bioinformatics approaches were adapted to investigate changes in the global protein profile of the damaged spinal cord tissue when experimental rats were treated either with or without aFGF at 24 h after injury. We found that 51 protein spots, resolvable by two-dimensional PAGE, had significant differential expression. Using hierarchical clustering analysis, these proteins were categorized into five major expression patterns. Noticeably proteins involved in the process of secondary injury, such as astrocyte activation (glial fibrillary acidic protein), inflammation (S100B), and scar formation (keratan sulfate proteoglycan lumican), which lead to the blocking of injured spinal cord regeneration, were down-regulated in the contusive spinal cord after treatment with aFGF. We propose that aFGF might initiate a series of biological processes to prevent or attenuate secondary injury and that this, Spinal cord injury (SCI)1 is a costly disease as well as the most frequent cause of mortality and morbidity in every medical care system around the world (1, 2). Traumatic axonal injury is a primary sequela of contusive SCI and is characterized by axonal swelling and disconnection of the ascending sensory and descending motor tracts (3). Contusive SCI seems to initiate a complicated cascade of pathophysiological changes, a process called secondary injury, including fiber deformation, increased vascular permeability, local ischemia, intraneuronal edema, and local demyelination. Moreover traumatic axonal injury typically involves a disruption of the axonal membrane, and this results in up-regulation of the entry of calcium, the influx of which initiates calpain activation (4, 5) and mitochondrial injury/swelling (6), resulting in cytochrome c release and caspase activation (7). Simultaneously the proliferation and hypertrophy of astrocytes around the injury site are characterized by increased immunoreactivity to glial fibrillary acidic proteins (GFAPs) (8).Although many studies have focused on revealing the pathophysiology of SCI, the exact molecular mechanisms and the biochemical pathways that mediate secondary injury remain sketchy (9). Spinal cord injury often causes permanent neurological deficits mostly because the injured neurons lack regenerative ability, and the series of destructive processes that follow SCI results in a second wave of cell death and spreading tissue loss (10). Therefore, studies of the stimulaFrom the ‡Institute

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Section: Confirmation Of the Differential Expression Of The Protein Gmentioning

confidence: 75%

Involvement of Acidic Fibroblast Growth Factor in Spinal Cord Injury Repair Processes Revealed by a Proteomics Approach

Tsai¹,

Shen²,

Kuo

et al. 2008

Molecular & Cellular Proteomics

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“…P ost-translational modifications in proteins participate in many fundamental cellular processes [1][2][3] and affect at least one-third of all eukaryotic proteins 4,5 . In particular, protein phosphorylation plays key roles in many signal-transduction processes [4][5][6][7][8] , preferentially targeting intrinsically disordered protein domains (IDPs) 4,5 .…”

mentioning

confidence: 99%

Kinetic modulation of a disordered protein domain by phosphorylation

2014

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Phosphorylation is a major post-translational mechanism of regulation that frequently targets disordered protein domains, but it remains unclear how phosphorylation modulates disordered states of proteins. Here we determine the kinetics and energetics of a disordered protein domain the kinase-inducible domain (KID) of the transcription factor CREB and that of its phosphorylated form pKID, using high-throughput molecular dynamic simulations. We identify the presence of a metastable, partially ordered state with a 60-fold slowdown in conformational kinetics that arises due to phosphorylation, kinetically stabilizing residues known to participate in an early binding intermediate. We show that this effect is only partially reconstituted by mutation to glutamate, indicating that the phosphate is uniquely required for the long-lived state to arise. This mechanism of kinetic modulation could be important for regulation beyond conformational equilibrium shifts.

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“…Advances in the field of proteomic analysis have significant implications for understanding the huge number of pathways that manage behaviour and cognition and nervous system response to disease or injury [41] . The analysis of Aβ and tau protein from the patients of AD helps to sought out the model and formation of toxic Aβ protein and p-tau [42] .…”

Section: Proteomics Of Aβ and Tau Proteinmentioning

confidence: 99%

Pathogenesis of Alzheimer's Disease: Role of Amyloid-beta and Hyperphosphorylated Tau Protein

Sajjad¹,

Arif²,

Shah³

et al. 2018

pharmaceutical-sciences

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Sajjad, et al.: Pathogenesis of Alzheimer's DiseaseThe pathological emblems of Alzheimer's disease are the accumulation of amyloid-β plaques and neurofibrillary tangles. The alluvium of toxic amyloid-β-protein in the form of aggregates is central to the pathogenesis of Alzheimer's disease. The aggregate formation is due to the structural refitting of α-helical sheet of normal, soluble amyloid-β-protein to the β-sheets, which lead to oligomeric, fibrillar, insoluble and disease causing amyloid-β 42. Mounting data suggests that another factor, the tau protein ripens into highly phosphorylated form by several kinases after Aβ-stimulation leads to tangle formation resulting in neuronal bereavement in hippocampus and entorhinal regions as the disease progresses further. An overview has been presented in this review of the role of tau as an important partner of amyloid-β in the pathogenesis of Alzheimer's disease, both of which could be used as biomarkers for diagnosis and risk assessment with other molecular chaperones, which are associated with Alzheimer's disease. As a part of common pathophysiological mechanism the understanding of amyloid-β and tau toxicities might be helpful for finding molecular targets for the prevention or even cure of Alzheimer's disease.

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Proteomic Analysis in the Neurosciences

Cited by 63 publications

References 57 publications

Involvement of Acidic Fibroblast Growth Factor in Spinal Cord Injury Repair Processes Revealed by a Proteomics Approach

Involvement of Acidic Fibroblast Growth Factor in Spinal Cord Injury Repair Processes Revealed by a Proteomics Approach

Kinetic modulation of a disordered protein domain by phosphorylation

Pathogenesis of Alzheimer's Disease: Role of Amyloid-beta and Hyperphosphorylated Tau Protein

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