Role of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in psychological stress and depression

Tsai, Shih‐Jen

doi:10.18632/oncotarget.19935

Cited by 27 publications

(21 citation statements)

References 97 publications

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“…The trkB signaling pathway involves many proteins that also possibly affect BDNF function. In addition, the proteolytic cleavage of proBDNF (a BDNF precursor with effects opposite to those of BDNF) to BDNF by plasmin determines the direction of BDNF action ( Lu et al, 2005 ; Tsai, 2017b ). Therefore, polymorphisms in the genes encoding proteins involved in the trkB or plasmin signaling pathway may interact with the BDNF Val66Met polymorphism to affect disease susceptibility ( Tsai, 2004a , 2007b ; Hwang et al, 2006 ).…”

Section: Bdnf Val66met Polymorphism and Gene–gene Interactiomentioning

confidence: 99%

Critical Issues in BDNF Val66Met Genetic Studies of Neuropsychiatric Disorders

Tsai

2018

Front. Mol. Neurosci.

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120

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Neurotrophins have been implicated in the pathophysiology of many neuropsychiatric diseases. Brain-derived neurotrophic factor (BDNF) is the most abundant and widely distributed neurotrophin in the brain. Its Val66Met polymorphism (refSNP Cluster Report: rs6265) is a common and functional single-nucleotide polymorphism (SNP) affecting the activity-dependent release of BDNF. BDNF Val66Met transgenic mice have been generated, which may provide further insight into the functional impact of this polymorphism in the brain. Considering the important role of BDNF in brain function, more than 1,100 genetic studies have investigated this polymorphism in the past 15 years. Although these studies have reported some encouraging positive findings initially, most of the findings cannot be replicated in following studies. These inconsistencies in BDNF Val66Met genetic studies may be attributed to many factors such as age, sex, environmental factors, ethnicity, genetic model used for analysis, and gene–gene interaction, which are discussed in this review. We also discuss the results of recent studies that have reported the novel functions of this polymorphism. Because many BDNF polymorphisms and non-genetic factors have been implicated in the complex traits of neuropsychiatric diseases, the conventional genetic association-based method is limited to address these complex interactions. Future studies should apply data mining and machine learning techniques to determine the genetic role of BDNF in neuropsychiatric diseases.

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Section: Bdnf Val66met Polymorphism and Gene–gene Interactiomentioning

confidence: 99%

Critical Issues in BDNF Val66Met Genetic Studies of Neuropsychiatric Disorders

Tsai

2018

Front. Mol. Neurosci.

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120

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“…It has been shown that exogenous tPA administration increases hippocampal BDNF levels and the conversion of pro‐BDNF to BDNF by plasmin is essential for LTP late‐phases . In addition, a defective tPA/plasmin/PAI‐1‐mediated BDNF maturation has been claimed to be involved in the manifestation of some brain pathologies, such as substance abuse and addiction, depression, and stress …”

Section: Plasminogen Activation System and The Regulation Of Bdnf Matmentioning

confidence: 99%

“…62,63 In addition, a defective tPA/plasmin/PAI-1-mediated BDNF maturation has been claimed to be involved in the manifestation of some brain pathologies, such as substance abuse and addiction, 64,65 depression, 66 and stress. 67 These data are not surprising given the fact that pro-BDNF and BDNF may have opposite effects on survival and function of CNS neurons.…”

Section: Pl a S Minog En Ac Tivati On Sys Tem And The Reg Ul Ati Onmentioning

confidence: 99%

Amyloid beta soluble forms and plasminogen activation system in Alzheimer’s disease: Consequences on extracellular maturation of brain‐derived neurotrophic factor and therapeutic implications

et al. 2018

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Summary Soluble oligomeric forms of amyloid beta (Aβ) play an important role in causing the cognitive deficits in Alzheimer’s disease (AD) by targeting and disrupting synaptic pathways. Thus, the present research is directed toward identifying the neuronal pathways targeted by soluble forms and, accordingly, develops alternative therapeutic strategies. The neurotrophin brain‐derived neurotrophic factor (BDNF) is synthesized as a precursor (pro‐BDNF) which is cleaved extracellularly by plasmin to release the mature form. The conversion from pro‐BDNF to BDNF is an important process that regulates neuronal activity and memory processes. Plasmin‐dependent maturation of BDNF in the brain is regulated by plasminogen activator inhibitor‐1 (PAI‐1), the natural inhibitor of tissue‐type plasminogen activator (tPA). Therefore, tPA/PAI‐1 system represents an important regulator of extracellular BDNF/pro‐BDNF ratio. In this review, we summarize the data on the components of the plasminogen activation system and on BDNF in AD. Moreover, we will hypothesize a possible pathogenic mechanism caused by soluble Aβ forms based on the effects on tPA/PAI‐1 system and on the consequence of an altered conversion from pro‐BDNF to the mature BDNF in the brain of AD patients. Translation into clinic may include a better characterization of the disease stage and future direction on therapeutic targets.

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“…PAI-1 is deposited in extracellular matrix, promotes the formation of lipoid and atheromatous plaque, thickens basement membranes, and hardens vessel walls, thus promoting the occurrence and development of vascular diseases ( 24 ). PAI-1 participates in the hydrolysis of brain-derived neurotrophic factor (BDNF) to regulate the growth and apoptosis of neurons, which are thought to be associated with depression ( 25 ). In addition, the tPA/PAI-1-plasmin system that involves PAI-1 can inhibit depressive behaviors induced by excitable neurotoxicity, which is caused by excessive activation of N-methyl-D-aspartic acid receptor (NMDA) ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of microRNA-17 in hippocampal tissues and blood from mice with depression up-regulates the expression of PAI-1 mRNA and protein

Lv¹,

Li²,

Gao³

et al. 2020

Braz J Med Biol Res

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This study determined the expression of plasminogen activator inhibitor-1 (PAI-1) and microRNA (miR)-17 in a mouse depression model. Forty male mice were divided evenly into control and depression groups. A chronic unpredictable mild stress (CUMS) model was constructed. qRT-PCR was used to determine the expression of PAI-1 mRNA and miR-17. Western blotting and ELISA were used to determine expression of PAI-1 protein. Dual luciferase reporter assay was carried out to identify direct interaction between miR-17 and PAI-1 mRNA. The mice with depression had elevated PAI-1 mRNA and protein in hippocampal tissues and blood. Expression of miR-17 was decreased in hippocampal tissues and blood from mice with depression. miR-17 bound with the 3 0-UTR of PAI-1 mRNA to regulate its expression. This study demonstrated that miR-17 expression in hippocampal tissues and blood from mice with depression was decreased while expression of PAI-1 mRNA and protein was up-regulated. miR-17 participated in depression in mice by regulating PAI-1.

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Role of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in psychological stress and depression

Cited by 27 publications

References 97 publications

Critical Issues in BDNF Val66Met Genetic Studies of Neuropsychiatric Disorders

Critical Issues in BDNF Val66Met Genetic Studies of Neuropsychiatric Disorders

Amyloid beta soluble forms and plasminogen activation system in Alzheimer’s disease: Consequences on extracellular maturation of brain‐derived neurotrophic factor and therapeutic implications

Decreased expression of microRNA-17 in hippocampal tissues and blood from mice with depression up-regulates the expression of PAI-1 mRNA and protein

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