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14-3-3 proteins in neurodegeneration

Authors:	Steinacker Petra Aitken Alastair Otto Markus

Institution:	^aDepartment of Neurology, University of Ulm, Helmholtzstr. 8/1, 89081 Ulm, Germany;^bISB, School of Biological Sciences, Darwin Building, Kings Buildings, University of Edinburgh, Edinburgh EH9 3JR, Scotland, UK

Abstract:	Among the first reported functions of 14-3-3 proteins was the regulation of tyrosine hydroxylase (TH) activity suggesting a possible involvement of 14-3-3 proteins in Parkinson's disease. Since then the relevance of 14-3-3 proteins in the pathogenesis of chronic as well as acute neurodegenerative diseases, including Alzheimer's disease, polyglutamine diseases, amyotrophic lateral sclerosis and stroke has been recognized. The reported function of 14-3-3 proteins in this context are as diverse as the mechanism involved in neurodegeneration, reaching from basal cellular processes like apoptosis, over involvement in features common to many neurodegenerative diseases, like protein stabilization and aggregation, to very specific processes responsible for the selective vulnerability of cellular populations in single neurodegenerative diseases.Here, we review what is currently known of the function of 14-3-3 proteins in nervous tissue focussing on the properties of 14-3-3 proteins important in neurodegenerative disease pathogenesis.

Keywords:	Abbreviations: TH tyrosine hydroxylase 3&prime UTR three prime untranslated region CSF cerebrospinal fluid 2D-PAGE two-dimensional polyacrylamide gel electrophoresis PD Parkinson disease AD Alzheimer disease CJD Creutzfeldt-Jakob disease MSA multiple system atrophy DRPLA dentatorubropallidoluysian atrophy SCA spinocerebellar ataxia HD Huntington disease ALS amyotrophic lateral sclerosis ARJP autosomal recessive juvenile parkinsonism DLB dementia with Lewy bodies vCJD variant Creutzfeldt-Jakob disease NCAM neural cell adhesion molecule NUDL nuclear distribution protein nudE-like 1 LTP long-term potentiation SNARE soluble N-ethylmaleimide-sensitive factor attachment protein receptor FOX forkhead box SRPK2 kinase specific for the serine/arginine (SR) family of splicing factors PPAR-γ peroxisome proliferator-activated receptor-γ GFAP glial fibrillary acidic protein JNK c-Jun N-terminal kinases AP-1 activator protein 1 LIF leukemia inhibitory factor Nox nicotinamide adenine dinucleotide phosphate oxidase ASK1 apoptosis signal-regulating kinase 1 PP2A protein phosphatase 2A SIAH seven in absentia homolog mTORC mammalian target of rapamycin complex ULK1 UNC-51-like kinase 1 AICAR 5-aminoimidazole-4-carboxyamide ribonucleoside TTP tristetraprolin BRF butyrate response factor ARE AU-rich element KSRP K-homology splicing regulator protein HDAC histone deacetylase HAP1 huntingtin-associated protein 1 hVps34 human vacuolar protein sorting 34 PGC-1α peroxisome proliferator-activated receptor gamma coactivator 1α HDBP2 huntington's disease binding protein 2 NF-L neurofilament light chain MPP+ 1-methyl-4-phenyl pyridinium LRRK2 leucine-rich repeat protein kinase 2 Aβ beta amyloid JIP-1 c-Jun N-terminal kinase-interactive protein-1
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