JNK and p38 stresskinases — degenerative effectors of signal-transduction-cascades in the nervous system

Mielke, Kirsten; Herdegen, Thomas

doi:10.1016/s0301-0082(99)00042-8

Cited by 463 publications

(339 citation statements)

References 139 publications

Supporting

Mentioning

325

Contrasting

Unclassified

Order By: Relevance

“…Among the main stress signaling pathways or central mediators in stress response to oxidative insults are the MAPK cascades, the PI3-kinase/AKT, the nuclear factor B (NF-B) signaling system, p53 activation and the heat shock protein response. In summary, accumulating evidence seemingly indicates a central role for the MAPK signaling cascade in neuronal survival and death during the development and the aging of the CNS, as well as in the pathology of neurodegenerative diseases [48,136,226].…”

Section: Mapk Signaling Under Oxidative Stressmentioning

confidence: 99%

“…However, accumulating evidence suggests that flavonoids interact selectively within MAPK signaling cascades [104,107]. This could have important implications with regard to their possible sites of action in neurons since members of the MAPK family are involved in signaling to neuronal survival, regeneration and death [48,136,228]. Indeed, recent reports on oxidative stress in primary striatal neurons demonstrated that flavonoids, in particular epicatechin and kaempferol, are able to attenuate the activation of extracellular signal-related kinases (ERK1/2) and JNK and protect against neuronal cell death [178].…”

Section: Biological and Cellular Propertiesmentioning

confidence: 99%

“…The molecular mechanisms underlying oxidative stress-induced neuronal damage are emerging and appear to involve an apoptotic mode of death in which ERK1/2 [175,196] and JNK [48,136,226] have been strongly implicated. Furthermore, there is strong evidence for involvement of mitochondrial defects in neurodegenerative diseases, with neuronal cell death arising directly from mitochondrially generated ROS, ATP depletion or activation of the mitochondrialdependent apoptotic pathways [48,202,226].…”

Section: Apoptosis Mitochondrial Function and Mapk Signal Transductionmentioning

confidence: 99%

“…For example, accumulating evidence suggests that flavonoids can interact selectively within MAPK signaling cascades in non-neuronal models [104,107]. This could have important implications with regard to their possible sites of action in neurons since members of the MAPK family are involved in signaling to neuronal survival, regeneration, and death [48,136,226].…”

Section: Flavonoids: Neuroprotective Agents In Vivo and In Vitro?mentioning

confidence: 99%

See 3 more Smart Citations

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Schroeter

Boyd

Spencer

et al. 2002

Neurobiology of Aging

308

178

View full text Add to dashboard Cite

Oxidative and nitrosative stress is increasingly associated with the pathology of neurodegeneration and aging. The molecular mechanisms underlying oxidative/nitrosative stress-induced neuronal damage are emerging and appear to involve a mode of death in which mitogen-activated protein kinase (MAPK) signaling pathways are strongly implicated. Thus, attention is turning towards the modulation of intracellular signaling as a therapeutic approach against neurodegeneration. Both endogenous and dietary agents have been suggested as potent modulators of intracellular signal transduction, e.g. nitric oxide and flavonoids, respectively. This review addresses recent findings on the biological effects of flavonoids and nitric oxide in neurodegeneration and aims to elucidate the rationale for their prospective use as modulators of cellular signal transduction. © 2002 Elsevier Science Inc. All rights reserved.Keywords: Apoptosis; Oxidative stress; Neuron; Flavonoids; MAP kinase; JNK; ERK; Epicatechin; Nitric oxide; Mitochondria; Redox status; Polyphenols Abbreviations: AKT, serine/threonine kinase (also known as protein kinase B); AP-1, activator protein-1; Apaf-1, apoptosis protease activating factor-1; ASK1, apoptosis signal-regulating kinase-1; Bad, Bcl-2/BclX Lassociated death promoting protein; Bax, pro-apoptotic protein of the Bcl-2 family; Bcl-2, B-cell lymphoma 2: protein with anti-apoptotic properties; BclX L , long form of Bclx: anti-apoptotic protein of the Bcl-2 family; Caspase, cysteinyl aspartic acid-protease; c-Jun, mammalian equivalent of Jun: part of the AP-1 transcription complex; CREB, cAMP response element binding protein; DIABLO/smac, mitochondria-related pro-apoptotic protein: inhibits XIAP; ERK1/2, extracellular signal-related kinase; Fas, CD95: member of the TNF receptor family; GSHST, glutathione Stransferase; JNK, c-Jun amino-terminal kinase; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase; MAPKKK, MAPKK kinase; MEK1/2, ERK1/2-specific MAPKK; MKK4/7, JNK-specific MAPKK; MSK1, mitogen-and stress-activated kinase-1; NF-B, nuclear factor of immunoglobulin k locus in B-cells; ONOO − , peroxynitrite anion; p53, pro-apoptotic tumor suppressor gene product; PI3-kinase, phosphoinositol 3-kinase; Ras, small G-protein; RNS, reactive nitrogen species; ROS, reactive oxygen species; RSK, pp90 ribosomal S6 kinase; SAPK, stressactivated protein kinase; XIAP, X-linked inhibitor of apoptosis: inhibits the activation of caspase-9

show abstract

Section: Mapk Signaling Under Oxidative Stressmentioning

confidence: 99%

Section: Biological and Cellular Propertiesmentioning

confidence: 99%

Section: Apoptosis Mitochondrial Function and Mapk Signal Transductionmentioning

confidence: 99%

Section: Flavonoids: Neuroprotective Agents In Vivo and In Vitro?mentioning

confidence: 99%

See 2 more Smart Citations

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Schroeter

Boyd

Spencer

et al. 2002

Neurobiology of Aging

308

178

View full text Add to dashboard Cite

show abstract

“…Recent results suggest that mitogen-activated protein kinase (MAP), cJun N-terminal kinases (JNK) and p38 are important regulators of the cell death program in post-mitotic neurons following survival-factor withdrawal (Mielke and Herdegen, 2000). Experiments with sympathetic neurons cultured in vitro, as well as with cerebellar granule neurons and differentiated pheochromocytoma 12 (PC12) cells, have demonstrated that JNK/c-Jun and p38 signaling can promote apoptosis following survival-factor withdrawal.…”

mentioning

confidence: 99%