The novel cytosolic RING finger protein dactylidin is up‐regulated in brains of patients with Alzheimer's disease

Abstract

Alzheimer's disease (AD) is characterized by a progressive degeneration of neurons along with deposition of amyloid plaques and the formation of neurofibrillary tangles. Neurodegeneration in AD follows both a spatial pattern of selective vulnerability and temporal staging of affected neurons. In order to address transcriptional changes associated with this selective vulnerability, we used subtractive hybridization of transcripts derived from human frontal cortex, which degenerates in late stages of AD, against transcripts of the inferior temporal cortex, which is affected both heavily and early in the course of AD. Moreover, we compared these to brain sections obtained from age-matched control subjects. We isolated a differentially expressed novel gene encoding a polypeptide that contained an amino-terminal C3HC4 RING finger domain, called dactylidin. It is ubiquitously expressed in all tissues examined and in situ hybridization of mouse brain sections revealed specific expression in neurons. Further, heterologous expression studies revealed a cytoplasmic localization of dactylidin and as all known cytoplasmic RING finger proteins function as ubiquitin protein ligases, an E3-like ligase function of dactylidin is probable. However, the up-regulation of dactylidin in highly vulnerable brain tissues of AD patients was confirmed by a quantitative PCR approach, suggesting that dactylidin may function early in the progression of neurodegenerative diseases.

Genetic polymorphisms and breast cancer risk: evidence from meta-analyses, pooled analyses, and genome-wide association studies

“…It is up-regulated in the inferior temporal lobes of Alzheimer disease patients compared with healthy controls [133].…”

Analyzing Microarray Data of Alzheimer's Using Cluster Analysis to Identify the Biomarker Genes

“…Identification of candidate genes could provide easily accessible biomarkers to monitor Alzheimer's, and these are SORL1, and APP, and APOE, the other 21 genes listed are related to other diseases but may also be found to be associated with Alzheimer's; these are transmembrane protein 59 [11], chaperonin containing TCP1 subunit 4 (delta) [12], insulin-like growth factor 2 receptor [13], splicing factor proline/glutamine-rich [14], peroxiredoxin 3 [15], ring finger protein 14 [16], iduronate 2-sulfatase [17], single-stranded DNA-binding protein 1 [18], spectrin repeat containing, nuclear envelope 2, thioredoxin-like 4A [19], syntaxin-binding protein 3 [20], SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 1, unc-51-like kinase 2 ( C. elegans ), ATP/GTP-binding protein 1, fatty-acid-binding protein 7, brain [21], calbindin 1, 28 kDa [22], H2A histone family, member Y [23], coatomer protein complex, subunit alpha [12], Sin3A-associated protein, 18 kDa [24], 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase, and synaptotagmin-binding, cytoplasmic RNA-interacting protein [25]. …”

Modulation of Poly(ADP-Ribose) Polymerase-1 (PARP-1)-Mediated Oxidative Cell Injury by Ring Finger Protein 146 (RNF146) in Cardiac Myocytes

“…A systematic search for downstream regulators of parthanathos identified RNF146 (also termed "Iduna") (9). In an independent line of studies, RNF146 (in this study, it was also called "dactylidin") was simultaneously identified as a differentially expressed protein in the vulnerable regions of the brain in Alzheimer's disease; in this study, its E3 ubiquitin ligase function was also suggested (18). The initial functional role of RNF146 was first demonstrated in neuronal models of cell death induced by NMDA receptor agonists.…”