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1.
Synapse ; 78(4): e22301, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38819491

RESUMEN

Neurological disorders (NDs) are diseases of the central and peripheral nervous systems that affect more than one billion people worldwide. The risk of developing an ND increases with age due to the vulnerability of the different organs and systems to genetic, environmental, and social changes that consequently cause motor and cognitive deficits that disable the person from their daily activities and individual and social productivity. Intrinsic factors (genetic factors, age, gender) and extrinsic factors (addictions, infections, or lifestyle) favor the persistence of systemic inflammatory processes that contribute to the evolution of NDs. Neuroinflammation is recognized as a common etiopathogenic factor of ND. The study of new pharmacological options for the treatment of ND should focus on improving the characteristic symptoms and attacking specific molecular targets that allow the delay of damage processes such as neuroinflammation, oxidative stress, cellular metabolic dysfunction, and deregulation of transcriptional processes. In this review, we describe the possible role of sodium phenylbutyrate (NaPB) in the pathogenesis of Alzheimer's disease, hepatic encephalopathy, aging, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis; in addition, we describe the mechanism of action of NaPB and its beneficial effects that have been shown in various in vivo and in vitro studies to delay the evolution of any ND.


Asunto(s)
Enfermedades del Sistema Nervioso , Fenilbutiratos , Humanos , Fenilbutiratos/uso terapéutico , Fenilbutiratos/farmacología , Animales , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/metabolismo
2.
Development ; 150(9)2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-37052186

RESUMEN

Newly synthesized membrane proteins pass through the secretory pathway, starting at the endoplasmic reticulum and packaged into COPII vesicles, to continue to the Golgi apparatus before reaching their membrane of residence. It is known that cargo receptor proteins form part of the COPII complex and play a role in the recruitment of cargo proteins for their subsequent transport through the secretory pathway. The role of cornichon proteins is conserved from yeast to vertebrates, but it is poorly characterized in plants. Here, we studied the role of the two cornichon homologs in the secretory pathway of the moss Physcomitrium patens. Mutant analyses revealed that cornichon genes regulate different growth processes during the moss life cycle by controlling auxin transport, with CNIH2 functioning as a specific cargo receptor for the auxin efflux carrier PINA, with the C terminus of the receptor regulating the interaction, trafficking and membrane localization of PINA.


Asunto(s)
Vesículas Cubiertas por Proteínas de Revestimiento , Proteínas de Transporte de Membrana , Animales , Transporte de Proteínas , Vesículas Cubiertas por Proteínas de Revestimiento/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Transporte Biológico/fisiología , Proteínas de la Membrana/metabolismo , Proteínas Portadoras/metabolismo , Aparato de Golgi/metabolismo , Saccharomyces cerevisiae/metabolismo
3.
Artículo en Inglés | MEDLINE | ID: mdl-30038900

RESUMEN

Syf1 is a tetratricopeptide repeat (TPR) protein implicated in transcription elongation, spliceosome conformation, mRNA nuclear-cytoplasmic export and transcription-coupled DNA repair. Recently, we identified the spliceosomal components of the human parasite Entamoeba histolytica, among them is EhSyf. Molecular predictions confirmed that EhSyf contains 15 type 1 TPR tandem α-antiparallel array motifs. Amoeba transformants carrying plasmids overexpressing HA-tagged or EhSyf silencing plasmids were established to monitor the impact of EhSyf on the splicing of several test Entamoeba transcripts. EhSyf Entamoeba transformants efficiently silenced or overexpressed the proteins in the nucleus. The overexpression or absence of EhSyf notably enhanced or blocked splicing of transcripts irrespective of the strength of their 3' splice site. Finally, the absence of EhSyf negatively affected the transcription of an intron-less transcript. Altogether our data suggest that EhSyf is a bona fide Syf1 ortholog involved in transcription and splicing.


Asunto(s)
Entamoeba histolytica/enzimología , Entamoeba histolytica/metabolismo , Proteínas Protozoarias/metabolismo , Empalme del ARN , ARN Mensajero/metabolismo , Secuencias de Aminoácidos , Entamoeba histolytica/genética , Regulación de la Expresión Génica , Conformación Proteica , Proteínas Protozoarias/genética , Secuencias Repetitivas de Aminoácido
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