Effects of JIP3 on epileptic seizures: Evidence from temporal lobe epilepsy patients, kainic-induced acute seizures and pentylenetetrazole-induced kindled seizures

Z, Wang; Chen, Y; Lu, Yaodong; Chen, X; Cheng, Liang; Mi, Xiujuan; Xu, Xin; Deng, Wanni; Zhang, Y; Wang, N; Li, J; Li, Yiduo; Wang, X

doi:10.1016/j.neuroscience.2015.05.008

Cited by 18 publications

(15 citation statements)

References 41 publications

(11 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Knockout of the JNK3 isoform diminished the seizure class acutely provoked by kainate administration (Brecht et al, 2005), while knockdown of JNK-interacting protein (JIP3) decreased JNK activation and kindling induced by chemoconvulsants (Wang et al, 2015). Our study appears to be the first to demonstrate that JNK is hyperactivated in chronic epilepsy, and that its pharmacological inhibition reduces spontaneous seizure frequency.…”

Section: Discussionmentioning

confidence: 99%

Antiepileptic action of c-Jun N-terminal kinase (JNK) inhibition in an animal model of temporal lobe epilepsy

et al. 2017

View full text Add to dashboard Cite

Several phosphorylation signaling pathways have been implicated in the pathogenesis of epilepsy arising from both genetic causes and acquired insults to the brain. Identification of dysfunctional signaling pathways in epilepsy may provide novel targets for antiepileptic therapies. We previously described a deficit in phosphorylation signaling mediated by p38 mitogen-activated protein kinase (p38 MAPK) that occurs in an animal model of temporal lobe epilepsy, and that produces neuronal hyperexcitability measured in vitro. We asked whether in vivo pharmacological manipulation of p38 MAPK activity would influence seizure frequency in chronically epileptic animals. Administration of a p38 MAPK inhibitor, SB203580, markedly worsened spontaneous seizure frequency, consistent with prior in vitro results. However, anisomycin, a non-specific p38 MAPK activator, significantly increased seizure frequency. We hypothesized that this unexpected result was due to activation of a related MAPK, c-Jun N-terminal kinase (JNK). Administration of JNK inhibitor SP600125 significantly decreased seizure frequency in a dose-dependent manner without causing overt behavioral abnormalities. Biochemical analysis showed increased JNK expression and activity in untreated epileptic animals. These results show for the first time that JNK is hyperactivated in an animal model of epilepsy, and that phosphorylation signaling mediated by JNK may represent a novel antiepileptic target.

show abstract

Section: Discussionmentioning

confidence: 99%

Antiepileptic action of c-Jun N-terminal kinase (JNK) inhibition in an animal model of temporal lobe epilepsy

et al. 2017

View full text Add to dashboard Cite

show abstract

“…1). Specifically, JIP1 and JIP3 are required for JNKs activation and neuronal death in response to a wide range of neurotoxic insults [18,20,42,[45][46][47][48][49][50][51][52][53]. In healthy neurons, JIP1 is bound by the Akt kinase, limiting access of JIP1 scaffold to JNK and preventing JNK activation.…”

Section: Restriction Of Jnks In Neuronsmentioning

confidence: 99%

Apoptotic cell death regulation in neurons

2019

View full text Add to dashboard Cite

Apoptosis plays a major role in shaping the developing nervous system during embryogenesis as neuronal precursors differentiate to become post‐mitotic neurons. However, once neurons are incorporated into functional circuits and become mature, they greatly restrict their capacity to die via apoptosis, thus allowing the mature nervous system to persist in a healthy and functional state throughout life. This robust restriction of the apoptotic pathway during neuronal differentiation and maturation is defined by multiple unique mechanisms that function to more precisely control and restrict the intrinsic apoptotic pathway. However, while these mechanisms are necessary for neuronal survival, mature neurons are still capable of activating the apoptotic pathway in certain pathological contexts. In this review, we highlight key mechanisms governing the survival of post‐mitotic neurons, while also detailing the physiological and pathological contexts in which neurons are capable of overcoming this high apoptotic threshold.

show abstract

“…Regarding this, it also has been reported that anisomycin mediates JNK activation through overexpression of JNK-interacting protein 3 (JIP3), a scaffold protein that is involved in the regulation of the apoptotic process [68]. Interestingly, Wang and colleagues reported a selective neuronal localization of JIP3 in TLE patients and in rodents after post-seizure [69]. Likewise, selective inhibition of JIP3 through the administration of a lentivirus (LV-375JIP3-RNAi) decreased seizure severity mediated by experimental convulsiveness [69].…”

Section: Temporal Lobe Epilepsymentioning

confidence: 99%

“…Interestingly, Wang and colleagues reported a selective neuronal localization of JIP3 in TLE patients and in rodents after post-seizure [69]. Likewise, selective inhibition of JIP3 through the administration of a lentivirus (LV-375JIP3-RNAi) decreased seizure severity mediated by experimental convulsiveness [69].…”

Section: Temporal Lobe Epilepsymentioning

confidence: 99%

Role of c-Jun N-Terminal Kinases (JNKs) in Epilepsy and Metabolic Cognitive Impairment

Busquets

Ettcheto

Cano

et al. 2019

IJMS

View full text Add to dashboard Cite

Previous studies have reported that the regulatory function of the different c-Jun N-terminal kinases isoforms (JNK1, JNK2, and JNK3) play an essential role in neurological disorders, such as epilepsy and metabolic-cognitive alterations. Accordingly, JNKs have emerged as suitable therapeutic strategies. In fact, it has been demonstrated that some unspecific JNK inhibitors exert antidiabetic and neuroprotective effects, albeit they usually show high toxicity or lack therapeutic value. In this sense, natural specific JNK inhibitors, such as Licochalcone A, are promising candidates. Nonetheless, research on the understanding of the role of each of the JNKs remains mandatory in order to progress on the identification of new selective JNK isoform inhibitors. In the present review, a summary on the current gathered data on the role of JNKs in pathology is presented, as well as a discussion on their potential role in pathologies like epilepsy and metabolic-cognitive injury. Moreover, data on the effects of synthetic small molecule inhibitors that modulate JNK-dependent pathways in the brain and peripheral tissues is reviewed.

show abstract

Effects of JIP3 on epileptic seizures: Evidence from temporal lobe epilepsy patients, kainic-induced acute seizures and pentylenetetrazole-induced kindled seizures

Cited by 18 publications

References 41 publications

Antiepileptic action of c-Jun N-terminal kinase (JNK) inhibition in an animal model of temporal lobe epilepsy

Antiepileptic action of c-Jun N-terminal kinase (JNK) inhibition in an animal model of temporal lobe epilepsy

Apoptotic cell death regulation in neurons

Role of c-Jun N-Terminal Kinases (JNKs) in Epilepsy and Metabolic Cognitive Impairment

Contact Info

Product

Resources

About