Nutrient-Deprivation Autophagy Factor-1 (NAF-1): Biochemical Properties of a Novel Cellular Target for Anti-Diabetic Drugs.

Nutrient-Deprivation Autophagy Factor-1 (NAF-1): Biochemical Properties of a Novel Cellular Target for Anti-Diabetic Drugs.

PLoS One. 2013; 8(5): e61202
Tamir S, Zuris JA, Agranat L, Lipper CH, Conlan AR, Michaeli D, Harir Y, Paddock ML, Mittler R, Cabantchik ZI, Jennings PA, Nechushtai R

Nutrient-deprivation autophagy factor-1 (NAF-1) (synonyms: Cisd2, Eris, Miner1, and Noxp70) is a [2Fe-2S] cluster protein immune-detected both in endoplasmic reticulum (ER) and mitochondrial outer membrane. It was implicated in human pathology (Wolfram Syndrome 2) and in BCL-2 mediated antagonization of Beclin 1-dependent autophagy and depression of ER calcium stores. To gain insights about NAF-1 functions, we investigated the biochemical properties of its 2Fe-2S cluster and sensitivity of those properties to small molecules. The structure of the soluble domain of NAF-1 shows that it forms a homodimer with each protomer containing a [2Fe-2S] cluster bound by 3 Cys and one His. NAF-1 has shown the unusual abilities to transfer its 2Fe-2S cluster to an apo-acceptor protein (followed in vitro by spectrophotometry and by native PAGE electrophoresis) and to transfer iron to intact mitochondria in cell models (monitored by fluorescence imaging with iron fluorescent sensors targeted to mitochondria). Importantly, the drug pioglitazone abrogates NAF-1’s ability to transfer the cluster to acceptor proteins and iron to mitochondria. Similar effects were found for the anti-diabetes and longevity-promoting antioxidant resveratrol. These results reveal NAF-1 as a previously unidentified cell target of anti-diabetes thiazolidinedione drugs like pioglitazone and of the natural product resveratrol, both of which interact with the protein and stabilize its labile [2Fe-2S] cluster. HubMed – depression


Personalized cognitive training in unipolar and bipolar disorder: a study of cognitive functioning.

Front Hum Neurosci. 2013; 7: 108
Preiss M, Shatil E, Cermáková R, Cimermanová D, Ram I

Patients with unipolar depressive disorder and in the depressive phase of bipolar disorder often manifest psychological distress and cognitive deficits, notably in executive control. We used computerized cognitive training in an attempt to reduce psychological affliction, improve everyday coping, and cognitive function. We asked one group of patients (intervention group) to engage in cognitive training three times a week, for 20?min each time, for eight consecutive weeks. A second group of patients (control group) received standard care only. Before the onset of training we administered to all patients self-report questionnaires of mood, mental and psychological health, and everyday coping. We also assessed executive control using a broad computerized neurocognitive battery of tests which yielded, among others, scores in Working Memory, Shifting, Inhibition, Visuomotor Vigilance, Divided Attention, Memory Span, and a Global Executive Function score. All questionnaires and tests were re-administered to the patients who adhered to the study at the end of training. When we compared the groups (between-group comparisons) on the amount of change that had taken place from baseline to post-training, we found significantly reduced depression level for the intervention group. This group also displayed significant improvements in Shifting, Divided Attention, and in the Global executive control score. Further exploration of the data showed that the cognitive improvement did not predict the improvements in mood. Single-group data (within-group comparisons) show that patients in the intervention group were reporting fewer cognitive failures, fewer dysexecutive incidents, and less difficulty in everyday coping. This group had also improved significantly on the six executive control tests and on the Global executive control score. By contrast, the control group improved only on the reports of cognitive failure and on working memory. HubMed – depression


Microarray analyses reveal novel targets of exercise-induced stress resistance in the dorsal raphe nucleus.

Front Behav Neurosci. 2013; 7: 37
Loughridge AB, Greenwood BN, Day HE, McQueen MB, Fleshner M

Serotonin (5-HT) is implicated in the development of stress-related mood disorders in humans. Physical activity reduces the risk of developing stress-related mood disorders, such as depression and anxiety. In rats, 6 weeks of wheel running protects against stress-induced behaviors thought to resemble symptoms of human anxiety and depression. The mechanisms by which exercise confers protection against stress-induced behaviors, however, remain unknown. One way by which exercise could generate stress resistance is by producing plastic changes in gene expression in the dorsal raphe nucleus (DRN). The DRN has a high concentration of 5-HT neurons and is implicated in stress-related mood disorders. The goal of the current experiment was to identify changes in the expression of genes that could be novel targets of exercise-induced stress resistance in the DRN. Adult, male F344 rats were allowed voluntary access to running wheels for 6 weeks; exposed to inescapable stress or no stress; and sacrificed immediately and 2 h after stressor termination. Laser capture micro dissection selectively sampled the DRN. mRNA expression was measured using the whole genome Affymetrix microarray. Comprehensive data analyses of gene expression included differential gene expression, log fold change (LFC) contrast analyses with False Discovery Rate correction, KEGG and Wiki Web Gestalt pathway enrichment analyses, and Weighted Gene Correlational Network Analysis (WGCNA). Our results suggest that physically active rats exposed to stress modulate expression of twice the number of genes, and display a more rapid and strongly coordinated response, than sedentary rats. Bioinformatics analyses revealed several potential targets of stress resistance including genes that are related to immune processes, tryptophan metabolism, and circadian/diurnal rhythms. HubMed – depression