c-Jun N-terminal kinase signaling regulates events associated with both health and degeneration in motoneurons

Newbern, Jason M.; Taylor, Anna; Robinson, Mac; Lively, MO; Milligan, Carolanne E.

doi:10.1016/j.neuroscience.2007.05.009

Cited by 21 publications

(13 citation statements)

References 102 publications

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“…Nonetheless, deletion of a single isoform, JNK1, disrupts axon tract maintenance in vivo (Chang et al 2003;Bjorkblom et al 2005). The role of JNKs in axonal polarity and initiation is further supported by many cell culture studies showing that JNK inhibition attenuates neuritogenesis (Leppa et al 1998;Waetzig and Herdegen 2003;Eom et al 2005;Oliva et al 2006;Newbern et al 2007). Numerous lines of evidence suggest this pathway is also important for axonal extension (Leppa et al 1998;Rosso et al 2005;Xiao et al 2006;Ciani and Salinas 2007;Eminel et al 2008).…”

Section: Jnk Signaling and Axon Elongationmentioning

confidence: 96%

Initiating and Growing an Axon

Polleux¹,

Snider²

2010

Cold Spring Harbor Perspectives in Biology

163

127

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The ability of neurons to form a single axon and multiple dendrites underlies the directional flow of information transfer in the central nervous system. Dendrites and axons are molecularly and functionally distinct domains. Dendrites integrate synaptic inputs, triggering the generation of action potentials at the level of the soma. Action potentials then propagate along the axon, which makes presynaptic contacts onto target cells. This article reviews what is known about the cellular and molecular mechanisms underlying the ability of neurons to initiate and extend a single axon during development. Remarkably, neurons can polarize to form a single axon, multiple dendrites, and later establish functional synaptic contacts in reductionist in vitro conditions. This approach became, and remains, the dominant model to study axon initiation and growth and has yielded the identification of many molecules that regulate axon formation in vitro (Dotti et al. 1988). At present, only a few of the genes identified using in vitro approaches have been shown to be required for axon initiation and outgrowth in vivo. In vitro, axon initiation and elongation are largely intrinsic properties of neurons that are established in the absence of relevant extracellular cues. However, the importance of extracellular cues to axon initiation and outgrowth in vivo is emerging as a major theme in neural development (Barnes and Polleux 2009). In this article, we focus our attention on the extracellular cues and signaling pathways required in vivo for axon initiation and axon extension.

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Section: Jnk Signaling and Axon Elongationmentioning

confidence: 96%

Initiating and Growing an Axon

Polleux¹,

Snider²

2010

Cold Spring Harbor Perspectives in Biology

163

127

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“…JNK is activated after injury to central or peripheral neurons. In the periphery, JNK inhibitors suppress cell death; however, they also inhibit the ability of the surviving neurons to regenerate their axons (206). The molecular details (i.e., JNK isoforms, signaling complexes, etc.)…”

Section: A Jnks and The Central Nervous Systemmentioning

confidence: 99%

Mammalian MAPK Signal Transduction Pathways Activated by Stress and Inflammation: A 10-Year Update

Kyriakis

Avruch

2012

Physiological Reviews

1,199

910

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The mammalian stress-activated families of mitogen-activated protein kinases (MAPKs) were first elucidated in 1994, and by 2001, substantial progress had been made in identifying the architecture of the pathways upstream of these kinases as well as in cataloguing candidate substrates. This information remains largely sound. Nevertheless, an informed understanding of the physiological and pathophysiological roles of these kinases remained to be accomplished. In the past decade, there has been an explosion of new work using RNAi in cells, as well as transgenic, knockout and conditional knockout technology in mice that has provided valuable insight into the functions of stress-activated MAPK pathways. These findings have important implications in our understanding of organ development, innate and acquired immunity, and diseases such as atherosclerosis, tumorigenesis, and type 2 diabetes. These new developments bring us within striking distance of the development and validation of novel treatment strategies. Herein we first summarize the molecular components of the mammalian stress-regulated MAPK pathways and their regulation as described thus far. We then review some of the in vivo functions of these pathways.

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“…On the one hand, local application of JNK inhibitors blocked the regeneration of explanted neurons from dorsal root ganglia, nodose ganglia, and sympathetic ganglia (Lindwall and Kanje 2005). Inhibition of JNK prevented axotomy-induced cell death of dopaminergic neurons of substantia nigra ) and central extrinsic motoneurons-but the surviving motoneurons could no longer regenerate their axons (Newbern et al 2007). Similarly, the JNK target cJun mediates the regeneration of facial nerve fibers by regulating the expression of molecules like CD44, galanin, or alpha/beta 1 integrins (Raivich et al 2004;Raivich and Behrens 2006).…”

Section: Neuronal Regenerationmentioning

confidence: 99%

JNK: A Stress-Activated Protein Kinase Therapeutic Strategies and Involvement in Alzheimer’s and Various Neurodegenerative Abnormalities

Mehan¹,

Meena²,

Sharma³

et al. 2010

J Mol Neurosci

155

102

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The c-Jun N-terminal kinase (JNKs), also known as stress-activated protein kinase (SAPK), is one such family of multifunctional-signaling molecules, activated in response to wide range of cellular stresses as well as in response to inflammatory mediators. JNKs regulate various processes such as brain development, repair, and memory formation; but on the other hand, JNKs are potent effectors of neuroinflammation and neuronal death. A large body of evidence indicates that JNK activity is critical for normal immune and inflammatory response. Indeed, aberrant activation of JNK has been implicated in the pathogenesis of Alzheimer's disease. Moreover, the JNK pathway is considered to be a key regulator of various inflammatory pathways which are activated during normal aging and Alzheimer's disease therapy as well as key regulator of pro-inflammatory cytokines biosynthesis at the transcriptional and translational levels, which makes different components of these pathway potential targets for the treatment of autoimmune and inflammatory diseases. Pharmacological inhibition of JNK has been demonstrated to attenuate microglial activation and the release of neurotoxic chemicals including pro-inflammatory cytokines. In this review, we provide an overview on implications and therapeutic strategies of JNK in neurodegenerative disorders.

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c-Jun N-terminal kinase signaling regulates events associated with both health and degeneration in motoneurons

Cited by 21 publications

References 102 publications

Initiating and Growing an Axon

Initiating and Growing an Axon

Mammalian MAPK Signal Transduction Pathways Activated by Stress and Inflammation: A 10-Year Update

JNK: A Stress-Activated Protein Kinase Therapeutic Strategies and Involvement in Alzheimer’s and Various Neurodegenerative Abnormalities

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