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Keywords = CALCB

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10 pages, 1413 KB  
Article
Genetic Dissection of Temperament Personality Traits in Italian Isolates
by Maria Pina Concas, Alessandra Minelli, Susanna Aere, Anna Morgan, Paola Tesolin, Paolo Gasparini, Massimo Gennarelli and Giorgia Girotto
Genes 2022, 13(1), 4; https://doi.org/10.3390/genes13010004 - 21 Dec 2021
Cited by 3 | Viewed by 6631
Abstract
Human personality (i.e., temperament and character) is a complex trait related to mental health, influenced by genetic and environmental factors. Despite the efforts performed during the past decades, its genetic background is only just beginning to be identified. With the aim of dissecting [...] Read more.
Human personality (i.e., temperament and character) is a complex trait related to mental health, influenced by genetic and environmental factors. Despite the efforts performed during the past decades, its genetic background is only just beginning to be identified. With the aim of dissecting the genetic basis of temperament, we performed a Genome-Wide Association Study (GWAS) on Cloninger’s Temperament and Character Inventory in 587 individuals belonging to different Italian genetic isolates. Data analysis led to the identification of four new genes associated with different temperament scales, such as Novelty Seeking (NS), Harm Avoidance (HA), and Reward Dependence (RD). In detail, we identified suggestive and significant associations between: MAGI2 (highest p-value = 9.14 × 10−8), a gene already associated with schizophrenia and depressive disorder, and the NS–Extravagance scale; CALCB (highest p-value = 4.34 × 10−6), a gene likely involved in the behavioral evolution from wild wolf to domestic dog, and the NS–Disorderliness scale; BTBD3 (highest p-value = 2.152 × 10−8), a gene already linked to obsessive–compulsive disorder, and the HA–Fatigability scale; PRKN (highest p-value = 8.27 × 10−9), a gene described for early onset Parkinson’s disease, and the RD scale. Our work provides new relevant insights into the genetics of temperament, helping to elucidate the molecular basis of psychiatric disorders. Full article
(This article belongs to the Special Issue Genetics of Psychiatric Disease and the Basics of Neurobiology)
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17 pages, 3211 KB  
Article
Selective Expression of a SNARE-Cleaving Protease in Peripheral Sensory Neurons Attenuates Pain-Related Gene Transcription and Neuropeptide Release
by Wanzhi Wang, Miaomiao Kong, Yu Dou, Shanghai Xue, Yang Liu, Yinghao Zhang, Weiwei Chen, Yanqing Li, Xiaolong Dai, Jianghui Meng and Jiafu Wang
Int. J. Mol. Sci. 2021, 22(16), 8826; https://doi.org/10.3390/ijms22168826 - 17 Aug 2021
Cited by 12 | Viewed by 4287
Abstract
Chronic pain is a leading health and socioeconomic problem and an unmet need exists for long-lasting analgesics. SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) are required for neuropeptide release and noxious signal transducer surface trafficking, thus, selective expression of the SNARE-cleaving light-chain protease [...] Read more.
Chronic pain is a leading health and socioeconomic problem and an unmet need exists for long-lasting analgesics. SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) are required for neuropeptide release and noxious signal transducer surface trafficking, thus, selective expression of the SNARE-cleaving light-chain protease of botulinum neurotoxin A (LCA) in peripheral sensory neurons could alleviate chronic pain. However, a safety concern to this approach is the lack of a sensory neuronal promoter to prevent the expression of LCA in the central nervous system. Towards this, we exploit the unique characteristics of Pirt (phosphoinositide-interacting regulator of TRP), which is expressed in peripheral nociceptive neurons. For the first time, we identified a Pirt promoter element and cloned it into a lentiviral vector driving transgene expression selectively in peripheral sensory neurons. Pirt promoter driven-LCA expression yielded rapid and concentration-dependent cleavage of SNAP-25 in cultured sensory neurons. Moreover, the transcripts of pain-related genes (TAC1, tachykinin precursor 1; CALCB, calcitonin gene-related peptide 2; HTR3A, 5-hydroxytryptamine receptor 3A; NPY2R, neuropeptide Y receptor Y2; GPR52, G protein-coupled receptor 52; SCN9A, sodium voltage-gated channel alpha subunit 9; TRPV1 and TRPA1, transient receptor potential cation channel subfamily V member 1 and subfamily A member 1) in pro-inflammatory cytokines stimulated sensory neurons were downregulated by viral mediated expression of LCA. Furthermore, viral expression of LCA yielded long-lasting inhibition of pain mediator release. Thus, we show that the engineered Pirt-LCA virus may provide a novel means for long lasting pain relief. Full article
(This article belongs to the Special Issue Advances in Clostridial and Related Neurotoxins)
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