Neuronal expression of AP-1 proteins in excitotoxic-neurodegenerative disorders and following nerve fiber lesions

Abstract

This review tries to survey the expression patterns of inducible transcription factors (ITFs) of the Jun (c-Jun, JunB, JunD) and Fos (c-Fos, FosB, Fra) families as well as of zinc finger proteins (Krox-20 and Krox-24) and their mRNAs following ischemia, epileptic seizures, hypoglycemia, axotomy and (programmed) neuronal death in the mammalian brain. Jun and Fos proteins or Jun/Fos-containing transcription complexes are also termed as AP-1 proteins or AP-1 complexes. So far, however, the genes encoding for Jun, Fos and Krox proteins have been included into the rather heterogeneous pool of immediate—early genes (IEGs). Therefore, we suggest the term ‘inducible transcription factors’ (ITF) with regard to their main functional features: (rapid) inducibility and control of transcription. In the first part of the review, we summarize the current knowledge on the organization and control of the jun, fos and krox promoters as well as about the molecular down-stream effects of their proteins. In the sections on general and focal ischemia, epileptic seizures and hypoglycemia, the review is focused on the formation of specific expression patterns that is the individual temporo-spatial expression of different ITFs following the same pathophysiological stimulus. Particular emphasis is put on the correlation of ITF expression with vulnerability and resistance of specific neuronal subpopulations. Furthermore, we have also reviewed the DNA-binding activity of AP-1 proteins in the adult rat brain and the pool of putative effector proteins following the above-mentioned stimulation paradigms. Subsequently, the less defined role of ITFs in the process of (programmed) neuronal death is discussed. The last section surveys the prolonged and selective expression of c-Jun in axotomized neurons and its relation to the expression of nitric oxide synthase.