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Homeostasis of Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
The processes of DA synthesis by TH and DDC and its transport into storage vesicles by VMATs have long been viewed as two separate and independent events. However, several lines of evidence, employing co-immunoprecipitation, overexpression, mutagenesis, and in vitro binding assays, revealed that VMAT2 and the DA biosynthetic enzymes are physically and functionally coupled at the synaptic vesicle membrane [69]. The coupling complex also includes scaffolding proteins such as 14-3-3 protein and synuclein. Although TH is commonly considered a cytosolic enzyme, it exists in both cytosolic and membrane-bound forms. Cytosolic TH is enriched in neuronal somato–dendritic compartments of the substantia nigra and ventral tegmental area, whereas membrane-bound TH is more common in brain areas enriched in axon terminals (e.g., striatum and nucleus accumbens).
Intracellular Peptide Turnover: Properties and Physiological Significance of the Major Peptide Hydrolases of Brain Cytosol
Published in Gerard O’Cuinn, Metabolism of Brain Peptides, 2020
Hui et al. provided evidence for two isozymes of c-AAP in chicken brain132. Two forms of the soluble enzyme designated SI and SII were separated by Bio Gel HTP® chromatography. SI is a monomer of 105,000 whereas SII is composed of two polypeptides of 100,000 and 25,000. The catalytic properties of both forms are similar, however tryptic peptide maps differ. Amino acid sequence of fragments was reported as not identical but homologous. Interestingly, sequence homology to a brain specific 14-3-3 protein was found. This protein is a protein kinase activator of tyrosine and tryptophan hydroxylases. The possible regulation of c-AAP has not been extensively explored. The purified monkey brain enzyme was stimulated four-fold by 1mM ATP + 4 mM Mg++133. This effect was due to a change in the Vmax of the enzyme. However phosphorylation was not the underlying mechanism since these investigators found a similar effect with non-hydrolyzable analogs of ATP and could find no evidence for phosphorylation. It was proposed that ATP activates by reversibly binding to a site on the enzyme. The enzyme can also be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase. In this case, phosphorylation leads to a decrease in enzymatic activity. It is not known how these changes relate to the regulation of c-AAP in vivo.
Dementia Associated with Medical Conditions
Published in Marc E. Agronin, Alzheimer's Disease and Other Dementias, 2014
The clinical picture of CJD, from initial symptoms through rapidly progressive decline and then death, takes an average of 6–12 months. Early symptoms may include fatigue, insomnia, anorexia, mood swings, apathy, and behavioral disturbances (Roos, 2008). Depression and psychosis are seen in approximately 10% of cases and may include detailed delusions and hallucinations. As the disease progresses, memory impairment, speech disturbances, visual impairment, gait ataxia, and cerebellar dysfunction become more prominent. Many individuals display prominent myoclonic jerks, incontinence, and hallucinations. In the terminal phase, patients develop akinetic mutism: they cannot move, speak, swallow, or respond to stimulation. MRI scans of the brain may show basal ganglia hyperintensities in T2-weighted images (Cambier et al., 2003). In 80% of cases, EEGs show periodic bursts of characteristic bifrontal sharp waves or triphasic waves, set against a slowed background rhythm (Drazkowski, 2008). The 14-3-3 protein is a biomarker for CJD seen in the cerebrospinal fluid of over 90% of individuals with CJD (Hsich et al., 1996). As with Alzheimer's disease, the only way to make a 100% accurate diagnosis of CJD is to examine brain tissue via biopsy or autopsy and look for spongiform changes. In addition to microscopic examination, brain tissue (and with variant CJD some researchers have looked at tonsillar tissue) can be stained with antibodies to prion proteins.
Serum 14-3-3η is a Marker that Complements Current Biomarkers for the Diagnosis of RA: Evidence from a Meta-analysis
Published in Immunological Investigations, 2022
Yue Wu, Ziwei Dai, Haili Wang, Hong Wang, Lingling Wu, Huayun Ling, Ying Zhu, Dongqing Ye, Bin Wang
The 14-3-3 protein was discovered in the neuronal proteins extracted from cattle brain tissues in 1976, there are 7 isoforms (α/β, ε, γ, η, τ, ζ, σ)(Maksymowych et al. 2014b). These proteins have a cup-shaped “amphipathic groove” that can interact with more than 200 proteins and participate in the regulation of a variety of important cell activities, including protein trafficking, cell cycle regulation, signal transduction, tumorigenesis, etc. (Maksymowych et al. 2014b; Zeng and Tan. 2018). Kilani et al. found that 14-3-3 protein subtypes were correlated with MMP-1 and MMP-3 (The members of matrix metalloproteinases (MMPs) which play an important role in degrading cartilage matrix), and their experimental results showed that the levels of 14-3-3η and 14-3-3-3γ were very high in the serum and synovial fluid (SF) of RA patients, especially in SF (Kilani et al. 2007). Another study showed that 14-3-3η levels in serum and SF of RA patients were related to radiological damage (Hammam et al. 2020). In addition, 14-3-3η levels were also related to disease activity in RA patients (Hirata et al. 2015).
Erzhi pills ameliorate cognitive dysfunction and alter proteomic hippocampus profiles induced by d -galactose and Aβ1–
40 injection in ovariectomized Alzheimer’s disease model rats
Published in Pharmaceutical Biology, 2021
Yongyan Xie, Bo Yan, Min Hou, Maofu Zhou, Chao Liu, Mengsheng Sun, Kun He, Cong Fang, Yaohui Chen, Liping Huang
Proteomics is further used to evaluate the efficacy of traditional Chinese medicine by screening proteins with a differential expression before and after treatment. In our study, hippocampal proteomics was used as a starting point, targeting the key pathological site of AD, followed by an exploration of the molecular mechanism of Erzhi pills in preventing AD by analyzing the changes in different proteins. We identified more than 100 differentially expressed proteins between the Erzhi pills group and the model group, which are involved in 48 signalling pathways. In addition, five types of proteins are involved in the PI3K/Akt signalling pathway (14-3-3, GSK3β, Akt, Ywhae, and Ywhag). As the downstream protein of the PI3K/Akt signalling pathway, the content of 14-3-3 protein was significantly increased. Based on the correlation with AD, the number of different proteins involved in the pathway, and the significant changes in protein expression, we speculate that Erzhi pills can regulate the PI3K/Akt signalling pathway by upregulating 14-3-3 protein expression, subsequently decreasing phosphorylation of tau and inducing neuronal apoptosis and ultimately relieving the pathological symptoms of AD.
Quercetin protects cardiomyocytes against doxorubicin-induced toxicity by suppressing oxidative stress and improving mitochondrial function via 14-3-3γ
Published in Toxicology Mechanisms and Methods, 2019
Xuanying Chen, Xiaoping Peng, Yong Luo, Jiegen You, Dong Yin, Qiang Xu, Huan He, Ming He
14-3-3γ is one of the 14-3-3 protein family members, which belong to a group of highly conserved 30 kDa acidic proteins that are expressed in a wide variety of organisms and tissues (Aitken 2006). 14-3-3 s participate in the regulation of diverse biological processes such as cell division, signal transduction, and apoptosis by interacting with their effector proteins (Fu et al. 2000; van Hemert et al. 2001). 14-3-3 s also play an important role in cardiac protection (Allouis et al. 2006; Lynn et al. 2008). Our previous studies confirmed that two members of the 14-3-3 protein family members, 14-3-3η and 14-3-3γ, are involved in myocardial injury and protection; 14-3-3η is involved in ischemia/hypoxia injury, whereas 14-3-3γ is involved in infection-related injury (He et al. 2006; Chen et al. 2007; Liu et al. 2014; He et al. 2018; Huang et al. 2018). In preliminary experiments, Que increased the expression of 14-3-3γ.