AP-1 proteins in the adult brain: facts and fiction about effectors of neuroprotection and neurodegeneration

Jun and Fos proteins are induced and activated following most physiological and pathophysiological stimuli in the brain. Only few data allow conclusio ns about distinct functions of AP-1 proteins in neurodegeneration and neuro regeneration, 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 destruct ion of the neuron-target-axis including withdrawal of trophic molecules. Th e inhibition of JNKs might exert neuroprotection by subsequent omission of c-Jun activation. Besides endogenous neuronal functions, the c-Jun/AP-1 pro teins can damage the nervous system by upregulation of harmful programs in non-neuronal cells (e,g, microglia) with release of neurodegenerative molec ules. In contrast, the differentiation with neurite extension and maturatio n of neural cells in vitro indicate physiological and potentially neuroprot ective functions of c-Jun and JNKs including sensoring for alterations in t he cytoskeleton, This review summarizes the multiple molecular interfunctio ns which are involved in the shift from the physiological role to degenerat ive effects of the Jun/JNK-axis such as cell type-specific expression and i ntracellular localization of scaffold proteins and upstream activators, ant agonistic phosphatases, interaction with other kinase systems, or the activ ation of transcription factors competing for binding to JNK proteins and AP -1 DNA elements.