NEURONAL EXPRESSION OF AP-1 PROTEINS IN EXCITOTOXIC-NEURODEGENERATIVEDISORDERS AND FOLLOWING NERVE-FIBER LESIONS

This review tries to survey the expression patterns of inducible trans cription 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 Kr ox-24) and their mRNAs following ischemia, epileptic seizures, hypogly cemia, axotomy and (programmed) neuronal death in the mammalian brain. Jun and Fos proteins of Jun/Fos-containing transcription complexes ar e also termed as AP-1 proteins of 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). Theref ore, we suggest the term 'inducible transcription factors' (ITF) with regard to their main functional features: (rapid) inducibility and con trol of transcription. In the first part of the review, we summarize t he current knowledge on the organization and control of the jun, fos a nd krox promoters as well as about the molecular down-stream effects o f their proteins. In the sections on general and focal ischemia, epile ptic seizures and hypoglycemia, the review is focused on the formation of specific expression patterns that is the individual temporo-spatia l expression of different ITFs following the same pathophysiological s timulus. Particular emphasis is put on the correlation of ITF expressi on with vulnerability and resistance of specific neuronal subpopulatio ns. Furthermore, we have also reviewed the DNA-binding activity of AP- 1 proteins in the adult rat brain and the pool of putative effector pr oteins following the above-mentioned stimulation paradigms. Subsequent ly, the less defined role of ITFs in the process of (programmed) neuro nal death is discussed. The last section surveys the prolonged and sel ective expression of c-Jun in axotomized neurons and its relation to t he expression of nitric oxide synthase.