AP-1 proteins in the adult brain: facts and fiction about effectors of neuroprotection and neurodegeneration
- 30 April 2001
- journal article
- review article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 20 (19), 2424-2437
- https://doi.org/10.1038/sj.onc.1204387
Abstract
Jun and Fos proteins are induced and activated following most physiological and pathophysiological stimuli in the brain. Only few data allow conclusions about distinct functions of AP-1 proteins in neurodegeneration and neuroregeneration, and these functions mainly refer to c-Jun and its activation by JNKs. Apoptotic functions of activated c-Jun affect hippocampal, nigral and primary cultured neurons following excitotoxic stimulation and destruction of the neuron-target-axis including withdrawal of trophic molecules. The inhibition of JNKs might exert neuroprotection by subsequent omission of c-Jun activation. Besides endogenous neuronal functions, the c-Jun/AP-1 proteins can damage the nervous system by upregulation of harmful programs in non-neuronal cells (e.g. microglia) with release of neurodegenerative molecules. In contrast, the differentiation with neurite extension and maturation of neural cells in vitro indicate physiological and potentially neuroprotective functions of c-Jun and JNKs including sensoring for alterations in the cytoskeleton. This review summarizes the multiple molecular interfunctions which are involved in the shift from the physiological role to degenerative effects of the Jun/JNK-axis such as cell type-specific expression and intracellular localization of scaffold proteins and upstream activators, antagonistic phosphatases, interaction with other kinase systems, or the activation of transcription factors competing for binding to JNK proteins and AP-1 DNA elements.This publication has 113 references indexed in Scilit:
- Molecular Cloning of Multiple Splicing Variants of JIP-1 Preferentially Expressed in BrainJournal of Neurochemistry, 2001
- A Scaffold Protein in the c-Jun NH2-terminal Kinase Signaling Pathways Suppresses the Extracellular Signal-regulated Kinase Signaling PathwaysOnline Journal of Public Health Informatics, 2000
- Overexpression of GluR6 in Rat Hippocampus Produces Seizures and Spontaneous Nonsynaptic Bursting in VitroNeurobiology of Disease, 2000
- Activation of MLK2-mediated Signaling Cascades by Polyglutamine-expanded HuntingtinOnline Journal of Public Health Informatics, 2000
- Stress-Induced Activation of c-Jun N-Terminal Kinase in Sensory Ganglion Neurons: Accumulation in Nuclear Domains Enriched in Splicing Factors and Distribution in Perichromatin FibrilsExperimental Cell Research, 2000
- Dynamics of Regional Brain Metabolism and Gene Expression After Middle Cerebral Artery Occlusion in MiceJournal of Cerebral Blood Flow & Metabolism, 2000
- Expression of c-fos, c-jun, and N-terminal kinase (JNK) in a Development Model of Induced Apoptotic Death in Neurons of the Substantia NigraJournal of Neurochemistry, 1999
- Axonal injury and peripheral nerve grafting in the thalamus and cerebellum of the adult rat: upregulation of c‐jun andcorrelation with regenerative potentialEuropean Journal of Neuroscience, 1998
- Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammationNature, 1997
- Block of c‐Fos and JunB Expression by Antisense Oligonucleotides Inhibits Light‐induced‐Phase Shifts of the Mammalian Circadian ClockEuropean Journal of Neuroscience, 1995