Plasminogen activator inhibitor-1 in the cerebrospinal fluid as an index of neurological disease

Sutton, Rosemary; Me, Keohane; VanderBerg,; Sl, Gonias

doi:10.1097/00001721-199404000-00002

Cited by 54 publications

(37 citation statements)

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“…However, in AD, tPA activity has been shown to be decreased in AD models, and its activity is proposed to be controlled by substantial increases in PAI-1 (64). In addition, PAI-1 protein levels increase in the CSF of AD patients (65), and PAI-1 mRNA is increased in APP transgenic mice (66). Brain plasmin activity was reported to also be reduced in AD brains (67).…”

Section: Discussionmentioning

confidence: 99%

Proteolytic Cleavage of Extracellular α-Synuclein by Plasmin

Kim

Choi

Park

et al. 2012

Journal of Biological Chemistry

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Background: A prion-like spread of ␣-synuclein might play a role in the pathogenesis of Parkinson disease. Results: Extracellular ␣-synuclein was cleaved by plasmin. Cultured microglia and astrocytes did not take up plasmin digested extracellular ␣-synuclein, and were not activated. Conclusion: Plasmin-mediated ␣-synuclein clearance problems might play a role in the pathogenesis of Parkinson disease. Significance: Therapies aimed at ␣-synuclein clearance may lead to new therapies for Parkinson disease.

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Section: Discussionmentioning

confidence: 99%

Proteolytic Cleavage of Extracellular α-Synuclein by Plasmin

Kim

Choi

Park

et al. 2012

Journal of Biological Chemistry

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“…Plasmin then cleaves A␤ with an efficiency that is approximately 10% that of plasmin toward its normal fibrin substrate (Tucker et al, 2000a). Interestingly, PAI-1, the principal physiologic inhibitor of tPA, and the less prominent PAI-2 are both increased during inflammation (Henkin et al, 1991) and have both been reported to be increased in AD (Akiyama et al, 1993;Sutton et al, 1994). Hence, we interpret these results as suggesting a feed-forward model in AD in which inflammation increases the expression of the plasminogen activator inhibitors, which in turn inhibit uPA and tPA, thereby reducing plasmin activity and allowing A␤ levels to increase, which may then fuel further inflammation.…”

Section: Discussionmentioning

confidence: 99%

Urokinase‐type plasminogen activator inhibits amyloid‐β neurotoxicity and fibrillogenesis via plasminogen

Tucker

Kihiko-Ehmann

Estus

2002

J of Neuroscience Research

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Amyloid-beta (Abeta) appears central to Alzheimer's disease (AD), aggregates spontaneously, and is neurotoxic to neurons in vitro. Recently, several groups reported a familial AD locus on chromosome 10. Here, we note that urokinase-type plasminogen activator (uPA) is located within this locus. Previously, we reported that uPA and its functional homolog, tissue-type plasminogen activator, are induced by Abeta treatment of neurons in vitro as well as in a mouse model of Abeta accumulation in vivo. Moreover, the target of plasminogen activators, plasmin, degraded nonaggregated and aggregated Abeta and modulated Abeta toxicity and deposition. Here, we have evaluated the effects of uPA and plasminogen on Abeta fibril formation and neurotoxicity. We report that the combination of uPA and plasminogen, but neither alone, inhibits Abeta toxicity, reduces Abeta deposition in vitro, and inhibits Abeta fibrillogenesis. We interpret these observations as suggesting that uPA represents a possible candidate gene for the chromosome 10 familial AD locus.

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“…Although these findings may render the involvement of the plasmin system in AD less likely and specific, some considerations should be addressed. Changes of t-PA or PAI-1 levels were described in patients suffering from inflammatory or infectious diseases and in cases of dementia (see Sutton et al 1994;Akenami et al 1997;Kwiecinski et al 2009). Reasons of such increase are not clear, however, it is conceivable to suppose that these changes reflect the activation of the fibrinolytic system due to the inflammatory paths that are not involved in CSF during AD (Sprengers and Kluft 1987;Pöllänen et al 1991).…”

Section: Discussionmentioning

confidence: 99%

“…) showed increased levels of PAI-1, however, in a rather unspecific way (Sutton et al 1994;Akenami et al 1997).…”

Section: Introductionmentioning

confidence: 87%