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1.
Genomics ; 111(4): 549-559, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-29545002

RESUMO

This article introduces an alignment-free clustering method in order to cluster all the 66 DORs sequentially diverse protein sequences. Two different methods are discussed: one is utilizing twenty standard amino acids (without grouping) and another one is using chemical grouping of amino acids (with grouping). Two grayscale images (representing two protein sequences by order pair frequency matrices) are compared to find the similarity index using morphology technique. We could achieve the correlation coefficients of 0.9734 and 0.9403 for without and with grouping methods respectively with the ClustalW result in the ND5 dataset, which are much better than some of the existing alignment-free methods. Based on the similarity index, the 66 DORs are clustered into three classes - Highest, Moderate and Lowest - which are seen to be best fitted for 66 DORs protein sequences. OR83b is the distinguished olfactory receptor expressed in divergent insect population which is substantiated through our investigation.


Assuntos
Proteínas de Drosophila/química , Receptores Odorantes/química , Alinhamento de Sequência/métodos , Animais , Análise por Conglomerados , Proteínas de Drosophila/classificação , Proteínas de Drosophila/genética , Drosophila melanogaster , Filogenia , Receptores Odorantes/classificação , Receptores Odorantes/genética
2.
J Biochem Mol Toxicol ; 33(4): e22274, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30506660

RESUMO

BACKGROUND: Cadmium is a nonessential toxic heavy metal, which enters the body easily and damages the cellular system. The sonic hedgehog (Shh) signaling pathway is one of the key regulatory pathways, which define neural growth and development. OBJECTIVES: This study aimed to explore how cadmium exposure affects neural activities, Shh signaling cascade, and its downstream target genes. METHODS: Total 18 male Wistar rats were randomly divided into two groups, control and test groups. Test rats were administered with 3 mg cadmium/kg body weight, while the control rats were treated with vehicle continuously for 28 days. Thereafter, rats were killed and the isolated brain samples were examined using oxidative stress assessment, histological and immunohistological behavioral assessment, polymerase chain reaction (PCR), and the comet assay. RESULTS: A disturbed oxidative balance, DNA damage, and an upregulated Shh signaling pathway were observed in cadmium-treated samples. Loss of structural integrity in cerebellum and loss of motor activity were observed in cadmium-treated rats.


Assuntos
Cádmio/toxicidade , Cerebelo/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Cerebelo/metabolismo , Cerebelo/patologia , Dano ao DNA , Proteínas Hedgehog/genética , Proteína Homeobox Nkx-2.2 , Imuno-Histoquímica , Masculino , Microscopia Confocal , Microscopia Eletrônica de Varredura , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Reação em Cadeia da Polimerase , Ratos Wistar
3.
J Neurosci Res ; 96(1): 53-62, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28631844

RESUMO

There are various theories to explain the pathophysiology of depression and support its diagnosis and treatment. The roles of monoamines, brain-derived neurotrophic factor (BDNF), and Wnt signaling are well researched, but sonic hedgehog (Shh) signaling and its downstream transcription factor Gli1 are not well studied in depression. Shh signaling plays a fundamental role in embryonic development and adult hippocampal neurogenesis and also involved in the growth of cancer. In this article, we summarize the evidence for the Shh signaling pathway in depression and the potential crosstalk of Shh with Wnt and BDNF. Antidepressants are known to upregulate the adult hippocampal neurogenesis to treat depression. Shh plays an important role in adult hippocampal neurogenesis, and its downstream signaling components regulate the synthesis of Wnt proteins. Moreover, the expression of Gli1 and Smo is downregulated in depression. BDNF and Wnt signaling are also regulated by various available antidepressants, so there is the possibility that Shh may be involved in the pathophysiology of depression. Therefore, the crosstalk between the Shh, Wnt, and BDNF signaling pathways is being discussed to identify the potential targets. Specifically, the potential role of the Shh signaling pathway in depression is explored as a new target for better therapies for depression.


Assuntos
Antidepressivos/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Proteínas Hedgehog/metabolismo , Via de Sinalização Wnt/fisiologia , Animais , Antidepressivos/administração & dosagem , Sistemas de Liberação de Medicamentos/tendências , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Receptor Cross-Talk/efeitos dos fármacos , Receptor Cross-Talk/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Via de Sinalização Wnt/efeitos dos fármacos
4.
Curr Cancer Drug Targets ; 20(5): 335-340, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-29295693

RESUMO

BACKGROUND: Complex central nervous system (CNS) is made up of neuronal cells and glial cells. Cells of central nervous system are able to regenerate after injury and during repairing. Sonic hedgehog pathway initiated by Shh-N a glycoprotein plays vital role in CNS patterning growth, development and now tumorigenesis. Nkx2.2 homeodomain transcription factor is an effecter molecule, which is positively regulated by Shh during normal growth. Nkx2.2 is essential for V3 domain specification during neural tube patterning at embryonic stage. MBP + oligodendrocytes are differentiated from progenitor cells which express Olig2. Nx2.2 is co-expressed with Olig2 in oligodendrocytes and is essential for later stage of oligodendrocyte maturation. OBJECTIVE: This review paper explores the potential role of Nkx2.2 transcription factor in glioblastoma development. CONCLUSION: Shh pathway plays a vital role in oligodendrocytes differentiation and Nkx2.2 transcription factor is essential for oligodendrocytes differentiation and maturation. Intriguingly, down regulation of Nkx2.2 transcription factor with aberrant Shh signaling pathway is reported in glioma samples. So here it is suggested that Nkx2.2 expression pattern could be used as a potential biomarker for the early diagnosis of glioma.


Assuntos
Neoplasias Encefálicas/patologia , Proteínas de Homeodomínio/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodomínio/genética , Humanos , Proteínas Nucleares , Fatores de Transcrição , Proteínas de Peixe-Zebra/genética
5.
Heliyon ; 5(5): e01600, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31193084

RESUMO

Nicotine is the most common and highly addictive drug of abuse, associated with several life-threatening diseases and high mortality. Nicotine abuse is the concerted effort to feel reward and fight depression in depressed individuals. The underlying mechanism of nicotine is to activate the brain reward system in the central nervous system and provide an antidepressant effect. Antidepressants provide their therapeutic effect by stimulating hippocampal neurogenesis, which can be correlated with brain derived neurotrophic factor (BDNF) expression in the hippocampus. BDNF interacts with Wnt/ß-catenin and sonic hedgehog (Shh) signalling cascade to stimulate hippocampal neurogenesis. Shh is the marker of hippocampal neurogenesis and also involved in the neuropathology of depression. But knowledge in this area to identify the potential therapeutic target is limited. In our study, we explored the role of BDNF, Wnt/ß-catenin and Shh signalling in depression and the involvement of these signalling pathways in providing an antidepressant effect by nicotine. Our investigations showed that chronic unpredictable mild stress induced depression results declined expression of BDNF, Wnt/ß-catenin, Shh and its downstream transcription factors GLI1/2/3 and NKX2.2 in the hippocampus of male Wistar rat. Moreover, we also observed that nicotine administration increased the expression of these signalling molecules in providing the antidepressant effects.

6.
Neuromolecular Med ; 21(3): 250-261, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31037465

RESUMO

Depression is one of the most prevalent and crucial public health problem connected to significant mortality and co-morbidity. Recently, numerous studies suggested that dietary flavanones exhibit neuroprotective and antidepressant effects against various psycho-physiological conditions including depression. The present study is focused on the antidepressant and neuroprotective effects of naringenin (NAR) and the involvement of sonic hedgehog (Shh) signaling in the chronic unpredictable mild stress (CUMS)-induced depression. Twenty-four male Wistar rats were randomly assigned into four groups: CON group (saline s.c.), NAR group (NAR 50 mg/kg, p.o.), CUMS group (subjected to CUMS along with saline p.o.), and CUMS + NAR group (NAR 50 mg/kg p.o. along with CUMS) for 28 days including 1-week pre-treatment with NAR. The results showed that NAR was found to inhibit behavioral abnormalities including increased despair in force swim test, and reduced locomotor activity caused by CUMS in open field test. Moreover, Morris water maze revealed that NAR also mitigates CUMS-associated cognitive impairment. In addition to the antidepressant-like effect, NAR mitigates morphological anomalies in the hippocampal CA1 region and cortex. Furthermore, we observed brain-derived neurotrophic factor (BDNF), Shh, GLI1, NKX2.2, and PAX6 were downregulated in the hippocampus of CUMS-exposed rats, which can be upregulated by NAR pre-treatment. GLI1 is main downstream signaling component of Shh signaling cascade, which further regulates the expression of homeodomain transcription factors PAX6 and NKX2.2.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Flavanonas/uso terapêutico , Proteínas Hedgehog/fisiologia , Deficiências da Aprendizagem/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Proteína GLI1 em Dedos de Zinco/fisiologia , Animais , Antidepressivos/farmacologia , Doença Crônica , Depressão/etiologia , Depressão/metabolismo , Depressão/prevenção & controle , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Comportamento Exploratório/efeitos dos fármacos , Flavanonas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/química , Hipocampo/efeitos dos fármacos , Proteína Homeobox Nkx-2.2 , Deficiências da Aprendizagem/etiologia , Deficiências da Aprendizagem/metabolismo , Deficiências da Aprendizagem/prevenção & controle , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Transtornos da Memória/prevenção & controle , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Fármacos Neuroprotetores/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Estresse Psicológico/fisiopatologia , Natação
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