Protease-activated receptors in the brain: Receptor expression, activation, and functions in neurodegeneration and neuroprotection

Luo, Weibo; Wang, Yingfei; Reiser, Georg

doi:10.1016/j.brainresrev.2007.08.002

Cited by 148 publications

(134 citation statements)

References 145 publications

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“…This possible dual effect of thrombin has been alluded to recently [Luo et al (2007) and references therein] and is a subject for further experimentation.…”

Section: Discussionmentioning

confidence: 80%

Thrombin Induces Long-Term Potentiation of Reactivity to Afferent Stimulation and Facilitates Epileptic Seizures in Rat Hippocampal Slices: Toward Understanding the Functional Consequences of Cerebrovascular Insults

Maggio¹,

Shavit²,

Chapman³

et al. 2008

J. Neurosci.

101

118

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The effects of thrombin, a blood coagulation serine protease, were studied in rat hippocampal slices, in an attempt to comprehend its devastating effects when released into the brain after stroke and head trauma. Thrombin acting through its receptor, protease-activated receptor 1 (PAR1), produced a long-lasting enhancement of the reactivity of CA1 neurons to afferent stimulation, an effect that saturated the ability of the tissue to undergo tetanus-induced long-term potentiation. This effect was mediated by activation of a PAR1 receptor, because it was shared by a PAR1 agonist, and was blocked by its selective antagonist. An independent effect of thrombin involved the lowering of the threshold for generating epileptic seizures in CA3 region of the hippocampus. Thus, the experiments in a slice mimicked epileptic and cognitive dysfunction induced by thrombin in the brain, and suggest that these effects are mediated by activation of the PAR1 receptor.

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“…This possible dual effect of thrombin has been alluded to recently [Luo et al (2007) and references therein] and is a subject for further experimentation.…”

Section: Discussionmentioning

confidence: 80%

Thrombin Induces Long-Term Potentiation of Reactivity to Afferent Stimulation and Facilitates Epileptic Seizures in Rat Hippocampal Slices: Toward Understanding the Functional Consequences of Cerebrovascular Insults

Maggio¹,

Shavit²,

Chapman³

et al. 2008

J. Neurosci.

101

118

View full text Add to dashboard Cite

show abstract

“…PAR are characterized by the presence of a tethered peptide ligand in their N‐terminal part which, when released by cleavage, acts on the ligand binding site and activates the receptor. The expression of PAR in the brain is differentially regulated in neurodegenerative disorders like PD, AD, multiple sclerosis and stroke (Luo, Wang, & Reiser, 2007). Activation of PAR can lead to cell death or cell survival, depending on the magnitude and the duration of agonist stimulation.…”

Section: Potential Therapeutic Targets In Astrocytesmentioning

confidence: 99%

Astroglia as a cellular target for neuroprotection and treatment of neuro‐psychiatric disorders

Liu

Teschemacher

Kasparov

2017

Glia

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Astrocytes are key homeostatic cells of the central nervous system. They cooperate with neurons at several levels, including ion and water homeostasis, chemical signal transmission, blood flow regulation, immune and oxidative stress defense, supply of metabolites and neurogenesis. Astroglia is also important for viability and maturation of stem‐cell derived neurons. Neurons critically depend on intrinsic protective and supportive properties of astrocytes. Conversely, all forms of pathogenic stimuli which disturb astrocytic functions compromise neuronal functionality and viability. Support of neuroprotective functions of astrocytes is thus an important strategy for enhancing neuronal survival and improving outcomes in disease states. In this review, we first briefly examine how astrocytic dysfunction contributes to major neurological disorders, which are traditionally associated with malfunctioning of processes residing in neurons. Possible molecular entities within astrocytes that could underpin the cause, initiation and/or progression of various disorders are outlined. In the second section, we explore opportunities enhancing neuroprotective function of astroglia. We consider targeting astrocyte‐specific molecular pathways which are involved in neuroprotection or could be expected to have a therapeutic value. Examples of those are oxidative stress defense mechanisms, glutamate uptake, purinergic signaling, water and ion homeostasis, connexin gap junctions, neurotrophic factors and the Nrf2‐ARE pathway. We propose that enhancing the neuroprotective capacity of astrocytes is a viable strategy for improving brain resilience and developing new therapeutic approaches.

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“…Cong Lin, 1 Jan von der Thüsen, 2 Joost Daalhuisen, 1 Marieke ten Brink, 1 Bruno Crestani, 3 Tom van der Poll, acute/chronic inflammatory and fibrotic diseases of the joints, skin, brain, lung and gastrointestinal tract (10,(12)(13)(14)(15).With respect to lung injury and pulmonary fibrosis, there is increasing evidence that PAR-2 is a critical contributor in the pathogenesis of IPF. Increased PAR-2 expression has been detected in the lungs of patients with IPF, and a recent study proposed that the PAR-2/tissue factor (TF)/FVIIa axis may contribute to the development and/or progression of IPF (16).…”

Section: Pharmacological Targeting Of Protease-activated Receptor 2 Amentioning

confidence: 99%

Pharmacological Targeting of Protease-Activated Receptor 2 Affords Protection from Bleomycin-Induced Pulmonary Fibrosis

Lin

Thüsen

Daalhuisen

et al. 2015

Mol Med

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Protease-activated receptors in the brain: Receptor expression, activation, and functions in neurodegeneration and neuroprotection

Cited by 148 publications

References 145 publications

Thrombin Induces Long-Term Potentiation of Reactivity to Afferent Stimulation and Facilitates Epileptic Seizures in Rat Hippocampal Slices: Toward Understanding the Functional Consequences of Cerebrovascular Insults

Thrombin Induces Long-Term Potentiation of Reactivity to Afferent Stimulation and Facilitates Epileptic Seizures in Rat Hippocampal Slices: Toward Understanding the Functional Consequences of Cerebrovascular Insults

Astroglia as a cellular target for neuroprotection and treatment of neuro‐psychiatric disorders

Pharmacological Targeting of Protease-Activated Receptor 2 Affords Protection from Bleomycin-Induced Pulmonary Fibrosis

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