Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

Terayama, Ryuji; Bandô, Yoshio; Murakami, Koichi; Kato, Keiko; Kishibe, Mari; Yoshida, Shigetaka

doi:10.1016/j.neuroscience.2007.05.037

Cited by 30 publications

(25 citation statements)

References 65 publications

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“…It was known that a larger amount of neuropsin, a serine protease, was found to be located in oligodendrocytes, and neuropsin-deficient mice showed alleviation of the severity of apoptosis of the oligodendrocytes (94). In addition to neuropsin, other serine proteases such as tissue-type plasminogen activator and matrix metalloproteinases also play a detrimental role in the pathology after CNS injury (95,96).…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…These data suggest that neuropsin is involved in the pathogenesis of EAE regulated by demyelination and oligodendroglial cell death. Similarly, neuropsin was recently shown to regulate demyelination, oligodendrocyte death, and axonal degeneration, thereby contributing to the secondary phase of the pathogenesis of spinal cord injury [88].…”

Section: Neuropsinmentioning

confidence: 97%

Trypsin and trypsin-like proteases in the brain: Proteolysis and cellular functions

Wang

Luo

Reiser

2007

Cell. Mol. Life Sci.

127

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Several serine proteases including thrombin, tissue-type plasminogen activator and urokinase-type plasminogen activator have been well characterized in the brain. In this article, we review the brain-related trypsin and trypsin-like serine proteases. Accumulating evidence demonstrates that trypsin and trypsin-like serine proteases play very important roles in neural development, plasticity, neurodegeneration and neuroregeneration in the brain. Neuropsin is able to hydrolyze the extracellular matrix components by its active site serine, and regulates learning and memory in normal brain. The mutant neurotrypsin contributes to mental retardation in children. Neurosin seems to be involved in the pathogenesis of neurodegenerative disorders, like Alzheimer's disease, Parkinson's disease or multiple sclerosis. Although mesotrypsin/trypsin IV is also implicated in neurodegeneration, its functional significance still remains largely unknown. Particularly, mesotrypsin/trypsin IV, P22 and neurosin exert their physiological and pathological functions through activation of certain protease-activated receptors (PARs). In the brain, the presence of serpins controls the activity of serine proteases. Therefore, understanding the interaction among brain trypsin, serpins and PARs will provide invaluable tools for regulating normal brain functions and for the clinical treatment of neural disorders.

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“…By affecting long-term potentiation KLK8 is believed to be involved in learning and memory [62]. There are also reports on a pathological role of KLK8 in neurodegenerative diseases [63]. Similarly, KLK6, which is alternatively named neurosin or zyme, is also reported to be involved in neurodegenerative disorders, such as Alzheimers disease, Parkinsons disease and multiple sclerosis [64][65][66][67][68].…”

Section: The Function Of Kallikrein-related Peptidasesmentioning

confidence: 99%

Kallikrein-related peptidases

Lundwall¹,

Brattsand²

2008

Cell. Mol. Life Sci.

132

111

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Kallikrein 1 (KLK1), a key component of the kallikrein-kinin system, originates from a locus on the long arm of chromosome 19 that contains several related serine endopeptidases. The biological role of these kallikrein-related peptidases is not clear, but emerging evidence suggests that they might be important in several physiological systems, e.g., in male reproduction, skin homeostasis, tooth enamel formation and neural development and plasticity. The kallikrein locus has undergone some major evolutionary events. Most spectacular are relatively recent duplications of KLK1 that have created 13 and 9 functional genes that are unique to the mouse and the rat, respectively. Human paralogs are KLK2 and KLK3: the latter encoding the cancer biomarker prostate-specific antigen. In this review on kallikrein-related peptidases, the focus is on their evolution, their role in skin homeostasis and semen liquefaction, and their utility as cancer biomarkers.

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Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

Cited by 30 publications

References 65 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

Trypsin and trypsin-like proteases in the brain: Proteolysis and cellular functions

Kallikrein-related peptidases

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