Role of plasminogen activator inhibitor‑1 in the diagnosis and prognosis of patients with Parkinson's disease

Pan, Hongxu; Zhao, Ying; Zhai, Zhengping; Zheng, Jinyu; Zhou, Yong; Zhai, Qijin; Cao, Xiangyang; Tian, Jinfeng; Zhao, Liandong

doi:10.3892/etm.2018.6076

Cited by 14 publications

(10 citation statements)

References 34 publications

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“…However, when chronically activated, microglia also contribute to neurodegenerative diseases by maintaining neuroinflammation. Several reports have indicated a role of PAI-1 in central nervous system pathology, including multiple sclerosis [ 130 , 131 ], Alzheimer’s disease [ 132 , 133 ], and Parkinson’s disease [ 134 , 135 ]. In demyelinated axons in inflammatory multiple sclerosis lesions, increased PAI-1 levels impair the capacity of the tPA/plasmin system to clear fibrin(ogen) deposits and therefore contribute to axonal damage in multiple sclerosis [ 131 , 136 ].…”

Section: Role Of Pai-1 In Diverse Pathologiesmentioning

confidence: 99%

A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: To Target or Not to Target?

Sillen

Declerck

2021

IJMS

110

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Plasminogen activator inhibitor-1 (PAI-1) is the main physiological inhibitor of plasminogen activators (PAs) and is therefore an important inhibitor of the plasminogen/plasmin system. Being the fast-acting inhibitor of tissue-type PA (tPA), PAI-1 primarily attenuates fibrinolysis. Through inhibition of urokinase-type PA (uPA) and interaction with biological ligands such as vitronectin and cell-surface receptors, the function of PAI-1 extends to pericellular proteolysis, tissue remodeling and other processes including cell migration. This review aims at providing a general overview of the properties of PAI-1 and the role it plays in many biological processes and touches upon the possible use of PAI-1 inhibitors as therapeutics.

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Section: Role Of Pai-1 In Diverse Pathologiesmentioning

confidence: 99%

A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: To Target or Not to Target?

Sillen

Declerck

2021

IJMS

110

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“…However, we have found that 3 of the ve PD-VPs that interact with it appear upregulated/signicantly-increased in blood (APP [84] and SERPINE1 [85]) or CSF (TGFB1 [86]) of PD patients. The other two PD-VPs are neuroprotective for PD (HGF [87] and TIMP1 [88]).…”

Section: Resultsmentioning

confidence: 76%

Cascading from SARS-CoV-2 to Parkinson's Disease through Protein-Protein Interactions

Estrada

2021

Preprint

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Background : Extensive extrapulmonary damages in a dozen of organs/systems, including the central nervous system (CNS), are reported in patients of the coronavirus disease 2019 (COVID-19). Three cases of Parkinson's disease (PD) have been reported as a direct consequence of COVID-19. In spite of the scarce data for establishing a definitive link between COVID-19 and PD some hypothesis have been proposed to explain the cases reported. They, however, do not fit well with the clinical findings reported for COVID-19 patients in general and for the PD cases reported in particular. Given the importance of this potential connection we present here a molecular-level mechanism that explain well these findings and will serve to explore the potential CNS damage in COVID-19 patients. Methods : A model explaining the cascade effects from COVID-19 to CNS is developed by using bioinformatic tools. It includes the post-translational modification of host proteins in the lungs by viral proteins, the transport of modified host proteins via exosomes out the lungs, and the disruption of protein-protein interaction in the CNS by these modified host proteins. Results : We found 44 proteins significantly expressed in the CNS which are associated with PD and whose interactions can be perturbed by 24 host proteins significantly expressed in the lungs. These 24 perturbators are found to interact with viral proteins and to form part of the cargoes of exosomes in human tissues. The joint set of perturbators and PD-vulnerable proteins form a tightly connected network with significantly more connections than expected by selecting a random cluster of proteins of similar size from the human proteome. Conclusions : The molecular-level mechanism presented here provides several routes for the cascading of effects from the lungs of COVID-19 patients to PD. In particular, the disruption of autophagy/ubiquitination processes appears as an important mechanism that triggers the generation of large amounts of exosomes containing perturbators in their cargo, which would insult several PD-vulnerable proteins, potentially triggering Parkinsonism in COVID-19 patients.

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“…There is not much information about the possible role that this host protein could have in PD. However, we have found that 3 of the five PD-VPs that interact with it appear upregulated/significantly-increased in blood (APP [ 119 ] and SERPINE1 [ 120 ]) or CSF (TGFB1 [ 121 ]) of PD patients. The other two PD-VPs are neuroprotective for PD (HGF [ 122 ] and TIMP1 [ 123 ]).…”

Section: Discussionmentioning

confidence: 99%

Cascading from SARS-CoV-2 to Parkinson’s Disease through Protein-Protein Interactions

Estrada

2021

Viruses

View full text Add to dashboard Cite

Extensive extrapulmonary damages in a dozen of organs/systems, including the central nervous system (CNS), are reported in patients of the coronavirus disease 2019 (COVID-19). Three cases of Parkinson’s disease (PD) have been reported as a direct consequence of COVID-19. In spite of the scarce data for establishing a definitive link between COVID-19 and PD, some hypotheses have been proposed to explain the cases reported. They, however, do not fit well with the clinical findings reported for COVID-19 patients, in general, and for the PD cases reported, in particular. Given the importance of this potential connection, we present here a molecular-level mechanistic hypothesis that explains well these findings and will serve to explore the potential CNS damage in COVID-19 patients. The model explaining the cascade effects from COVID-19 to CNS is developed by using bioinformatic tools. It includes the post-translational modification of host proteins in the lungs by viral proteins, the transport of modified host proteins via exosomes out the lungs, and the disruption of protein-protein interaction in the CNS by these modified host proteins. Our hypothesis is supported by finding 44 proteins significantly expressed in the CNS which are associated with PD and whose interactions can be perturbed by 24 host proteins significantly expressed in the lungs. These 24 perturbators are found to interact with viral proteins and to form part of the cargoes of exosomes in human tissues. The joint set of perturbators and PD-vulnerable proteins form a tightly connected network with significantly more connections than expected by selecting a random cluster of proteins of similar size from the human proteome. The molecular-level mechanistic hypothesis presented here provides several routes for the cascading of effects from the lungs of COVID-19 patients to PD. In particular, the disruption of autophagy/ubiquitination processes appears as an important mechanism that triggers the generation of large amounts of exosomes containing perturbators in their cargo, which would insult several PD-vulnerable proteins, potentially triggering Parkinsonism in COVID-19 patients.

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Role of plasminogen activator inhibitor‑1 in the diagnosis and prognosis of patients with Parkinson's disease

Cited by 14 publications

References 34 publications

A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: To Target or Not to Target?

A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: To Target or Not to Target?

Cascading from SARS-CoV-2 to Parkinson's Disease through Protein-Protein Interactions

Cascading from SARS-CoV-2 to Parkinson’s Disease through Protein-Protein Interactions

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