Pallidin protein in neurodevelopment and its relation to the pathogenesis of schizophrenia
نویسندگان
چکیده
Pallidin is a protein found throughout the nervous system and it has been linked to the development of schizophrenia. At the same time, it has been suggested that schizophrenia is a neurodevelopmental disease. The p38 protein participates in neuronal differentiation and apoptosis. We hypothesized pallidin and p38 play a role in neural system development and the pathogenesis of schizophrenia, and designed several experiments to test this possibility. During pull-down experiments GST-pallidin was able to bind His-Ndn (an HDAC3 binding protein) in vitro. In cells co-transfected with HDAC3 and p38, the transcriptional activity of p38 was significantly inhibited by HDAC3. When pallidin was overexpressed, the transcriptional activity of the endogenous HDAC3 improved significantly. Overexpression of pallidin-EGFP in HCT116 p38 wild-type cells increased the endogenous p21 protein and the mRNA levels. The decrease in the expression of endogenous p38 affected the differentiation of N2a cells. The lengths of the neurites generated in the experimental group were significantly shorter than those in the control group. We conclude that pallidin indirectly regulates the transcriptional activity of p38 during neurodevelopment by binding HDAC3 and changing its cellular localization, which leaves p38 uninhibited. Moreover, since pallidin can also affect neuronal differentiation and its variants seem to be related to an increased risk of schizophrenia, it is possible that both pallidin and p38 play a role in the pathogenesis of the disease.
منابع مشابه
Correlation Between Immunohistochemical Profile of Giant Cell Granuloma with Pathogenesis and Biologic Behavior: A Review Article
Abstract: Background and Aim: Giant cell Granulomas (central and peripheral) are two fairly common lesions of the oral cavity with uncertain etiology and pathogenesis. As well, the reason for their different biologic behavior is not well understood yet. This study aimed to review the immunohistochemical profile of giant cell granuloma and its correlation with pathogenesis and biologic behavior....
متن کاملA distinct serum protein pattern in patients with paranoid schizophrenia
Introduction: Schizophrenia is a chronic mental illness, whose aetiology is still unclear; therefore, information about differences in serum protein patterns may improve the understanding of the pathophysiology of schizophrenia. The goal of this study was to use the proteomic approach to identify altered protein levels in the serum samples from patients with schizophrenia. Methods: Blood wa...
متن کاملReinvestigation of the dysbindin subunit of BLOC-1 (biogenesis of lysosome-related organelles complex-1) as a dystrobrevin-binding protein.
Dysbindin was identified as a dystrobrevin-binding protein potentially involved in the pathogenesis of muscular dystrophy. Subsequently, genetic studies have implicated variants of the human dysbindin-encoding gene, DTNBP1, in the pathogeneses of Hermansky-Pudlak syndrome and schizophrenia. The protein is a stable component of a multisubunit complex termed BLOC-1 (biogenesis of lysosome-related...
متن کاملRare association of schizophrenia and unilateral Graves’ disease with contralateral thyroid hemiagenesis in two cases of McCune-Albright syndrome
The classical triad of McCune-Albright syndrome (MAS) consists of polyostotic fibrous dysplasia (FD), skin hyperpigmentation (café-au-lait spots), and endocrine dysfunction, frequently seen in females as precocious puberty. Etiology is genetically based and is explained by mosaicism of activating somatic mutations of the alpha-subunit of Gs protein. Clinical presentation is varied and is depend...
متن کاملAssociation of Candidate Single Nucleotide Polymorphisms Related to Candidate Genes in Patients With Schizophrenia
Introduction: Schizophrenia is a chronic heterogenic neurodevelopment disorder. Many genes interfere in the development of SCZ. All four genes, NrCAM, PRODH, ANK3, and ANKK1, which were evaluated in this study, were previously reported to be associated with Schizophrenia. The NrCAM contributes to creating cognitive deficiencies through the CAM’s signaling pathway. PRODH plays a vital role in cr...
متن کامل