Alpha- and Beta-Synucleins mRNA Expression in Lymphocytes of Schizophrenia Patients

Noori–Daloii, Mohammad Reza; Kheirollahi, Majid; Mahbod, Parinaz; Mohammadi, Fatemeh; Astaneh, Ali Nazeri; Zarindast, Mohammad Reza; Azimi, C; Mohammadi, Mohammad Reza

doi:10.1089/gtmb.2010.0050

Cited by 15 publications

(11 citation statements)

References 25 publications

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“…Additionally, Ingenuity Global Functional Analysis revealed significant enrichment of the identified protein dataset for proteins previously shown to be linked to schizophrenia, including GAP43 [71], VDAC1 [72] and SNCB [73], all of which have been shown to play a role in synaptic communication. These results underscore the association between normal adolescent brain development and pathology.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the adolescent and adult mouse prefrontal cortex proteome

et al. 2017

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Adolescence is a developmental period characterized by unique behavioral phenotypes (increased novelty seeking, risk taking, sociability and impulsivity) and increased risk for destructive behaviors, impaired decision making and psychiatric illness. Adaptive and maladaptive adolescent traits have been associated with development of the medial prefrontal cortex (mPFC), a brain region that mediates regulatory control of behavior. However, the molecular changes that underlie brain development and behavioral vulnerability have not been fully characterized. Using high-throughput 2D DIGE spot profiling with identification by MALDI-TOF mass spectrometry, we identified 62 spots in the PFC that exhibited age-dependent differences in expression. Identified proteins were associated with diverse cellular functions, including intracellular signaling, synaptic plasticity, cellular organization and metabolism. Separate Western blot analyses confirmed age-related changes in DPYSL2, DNM1, STXBP1 and CFL1 in the mPFC and expanded these findings to the dorsal striatum, nucleus accumbens, motor cortex, amygdala and ventral tegmental area. Ingenuity Pathway Analysis (IPA) identified functional interaction networks enriched with proteins identified in the proteomics screen, linking age-related alterations in protein expression to cellular assembly and development, cell signaling and behavior, and psychiatric illness. These results provide insight into potential molecular components of adolescent cortical development, implicating structural processes that begin during embryonic development as well as plastic adaptations in signaling that may work in concert to bring the cortex, and other brain regions, into maturity.

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Section: Discussionmentioning

confidence: 99%

Comparison of the adolescent and adult mouse prefrontal cortex proteome

et al. 2017

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“…α-Synuclein is a small, soluble protein consisting of 140 amino acid residues [ 1 , 2 ] that is mainly synthesized in the central nervous system [ 3 , 4 ], but can also be found in the periphery; for example, in erythroid cells [ 5 , 6 ], platelets [ 7 , 8 ], and lymphocytes [ 9 ]. The physiological role of α-synuclein is highly diverse: it is assigned to microtubule-associated activity [ 10 ], antioxidant activity in membranes [ 11 ], has a role in neuronal plasticity [ 12 ], functions as a molecular chaperone in the formation of SNARE-complexes [ 13 ], and is involved in the functioning of the Golgi apparatus and transport vesicles [ 14 ], among others.…”

Section: Introductionmentioning

confidence: 99%

Investigation of α-Synuclein Amyloid Fibrils Using the Fluorescent Probe Thioflavin T

Sulatskaya

Rodina

Sulatsky

et al. 2018

IJMS

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In this work, α-synuclein amyloid fibrils—the formation of which is a biomarker of Parkinson’s disease—were investigated using the fluorescent probe thioflavin T (ThT). The experimental conditions of protein fibrillogenesis were chosen so that a sufficient number of continuous measurements could be performed to characterize and analyze all stages of this process. The reproducibility of fibrillogenesis and the structure of the obtained aggregates (which is a critical point for further investigation) were proven using a wide range of physical-chemical methods. For the determination of ThT-α-synuclein amyloid fibril binding parameters, the sample and reference solutions were prepared using equilibrium microdialysis. By utilizing absorption spectroscopy of these solutions, the ThT-fibrils binding mode with a binding constant of about 104 M−1 and stoichiometry of ThT per protein molecule of about 1:8 was observed. Fluorescence spectroscopy of the same solutions with the subsequent correction of the recorded fluorescence intensity on the primary inner filter effect allowed us to determine another mode of ThT binding to fibrils, with a binding constant of about 106 M−1 and stoichiometry of about 1:2500. Analysis of the photophysical characteristics of the dye molecules bound to the sites of different binding modes allowed us to assume the possible localization of these sites. The obtained differences in the ThT binding parameters to the amyloid fibrils formed from α-synuclein and other amyloidogenic proteins, as well as in the photophysical characteristics of the bound dye, confirmed the hypothesis of amyloid fibril polymorphism.

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“…Consequently, in this pilot study, we explore a group of candidate genes comprising the described risk genes known in the literature (Faraone and Mick 2010;Gizer et al 2009), and corticotropin-releasing factor binding protein (CRHBP) was selected as a response to stress, which is also thought to be a risk factor for ADHD, to assess their expression profile in peripheral blood samples taken from adult ADHD subjects compared with samples from healthy controls. Such concept was previously reported in which transcriptional profiling resulted in identification of several candidate genes in blood and brain, especially for schizophrenic patients Tsuang et al 2005;Mehler-Wex et al 2006;Noori-Daloii et al 2010;Taurines et al 2010) and Alzheimer's and Parkinson's disease patients (Grünblatt et al 2009(Grünblatt et al , 2010Scherzer et al 2007). …”

Section: Introductionmentioning

confidence: 90%

Pilot study: potential transcription markers for adult attention-deficit hyperactivity disorder in whole blood

Grünblatt

Geißler

Jacob

et al. 2012

ADHD Atten Def Hyp Disord

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Attention-deficit hyperactivity disorder (ADHD) is a common behavioural disorder that affects not only children and adolescents but also adults; however, diagnosis of adult ADHD is difficult because patients seem to have reduced externalized behaviour. ADHD is a multifactorial disorder in which many genes, all with small effects, are thought to cause the disorder in the presence of unfavourable environmental conditions. Therefore, in this pilot study, we explored the expression profile of a list of previously established candidate genes in peripheral blood samples from adult ADHD subjects (n = 108) and compared these results with those of healthy controls (n = 35). We demonstrate that combining the gene expression levels of dopamine transporter (SLC6A3), dopamine D5 receptor, tryptophan hydroxylase-1, and SNAP25 as predictors in a regression model resulted in sensitivity and specificity of over 80 % (ROC: max R 2 = 0.587, AUC = 0.917, P \ 0.001, 95 % CI: 0.900-0.985). In conclusion, the combination of these four genes could represent a potential method for estimating risk and could be of diagnostic value for ADHD. Nevertheless, further investigation in a larger independent population including different subtypes of ADHD (inattentive, hyperactive, or combined type) patients is required to obtain more specific sets of biomarkers for each subtype as well as to differentiate between child, adolescent, and adulthood forms.Edna Grünblatt and Julia Geißler have contributed equally.Electronic supplementary material The online version of this article

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Alpha- and Beta-Synucleins mRNA Expression in Lymphocytes of Schizophrenia Patients

Cited by 15 publications

References 25 publications

Comparison of the adolescent and adult mouse prefrontal cortex proteome

Comparison of the adolescent and adult mouse prefrontal cortex proteome

Investigation of α-Synuclein Amyloid Fibrils Using the Fluorescent Probe Thioflavin T

Pilot study: potential transcription markers for adult attention-deficit hyperactivity disorder in whole blood

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