Deciphering alterations in the expression of acetylcholinesterase in Alzheimer’s disease (Q3158826): Difference between revisions
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(Created claim: summary (P836): Ache is a polymorphic enzyme with different variants of splicing and molecular forms. Dr. Dr. García Ayllón has shown that in the brain of Alzheimer’s patients (AD) despite the decrease in enzymatic activity, AChE protein levels do not decrease due to a greater contribution of inactive or low-activity AChE forms. It has also described an increase in the expression of the noncholinergic variant AChE-R, which increases in situations of stress and...) |
(Changed label, description and/or aliases in en: translated_label) |
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Deciphering alterations in the expression of acetylcholinesterase in Alzheimer’s disease | |||
Revision as of 16:12, 12 October 2021
Project Q3158826 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | Deciphering alterations in the expression of acetylcholinesterase in Alzheimer’s disease |
Project Q3158826 in Spain |
Statements
41,000.0 Euro
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82,000.0 Euro
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50.0 percent
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1 January 2018
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31 March 2021
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FUNDACION PARA EL FOMENTO DE LA INV. SANITARIA Y BIOMEDICA DE LA COMUNIDAD VALENCIANA (FISABIO)
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38°15'55.19"N, 0°41'55.82"W
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03065
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AChE es una enzima polimórfica con diferentes variantes de splicing y formas moleculares. La Dra. García Ayllón ha demostrado que en cerebro de enfermos de Alzheimer (EA) a pesar del descenso de actividad enzimática los niveles de proteína AChE no disminuyen por una mayor contribución de formas AChE inactivas o de baja actividad. Además ha descrito un incremento de la expresión de la variante no colinérgica AChE-R, que aumenta en situaciones de estrés e inflamación. Por ello pensamos que AChE en la EA sufre una regulación compleja tanto a nivel molecular como post-traduccional probablemente consecuencia del papel fisilogico de cada forma de la enzima. Por ello en este proyecto de investigación se pretende analizar los mecanismos moleculares que podrían afectar a la expresión de AChE en la EA, analizando en cerebro de pacientes EA la metilación del promotor de AChE y los niveles de factores de que controlan el splicing de las diferentes variantes. También se analizarán los niveles de miR-132 que se ha visto que regula AChE y la regulación de su promotor como desencadenante de su afectación en la EA. En cultivos celulares analizaremos si la sobreexpresión de P-tau y el tratamiento con Aß afectan a la actividad del promotor de AChE y factores de splicing. Por otro lado, se investigarán la afectación en el proceso de glicosilación de la enzima como responsable del aumento de formas inactivas en la EA. Para ello se determinará la glicosilación de AChE en cerebro de EA mediante interacción con lectinas y los niveles de glicosiltransferas implicadas, profundizando en el papel de Aß en dicha alteración. También analizaremos la posible implicación de PS1 en su faceta de chaperona en la glicosilación de AChE. (Spanish)
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Ache is a polymorphic enzyme with different variants of splicing and molecular forms. Dr. Dr. García Ayllón has shown that in the brain of Alzheimer’s patients (AD) despite the decrease in enzymatic activity, AChE protein levels do not decrease due to a greater contribution of inactive or low-activity AChE forms. It has also described an increase in the expression of the noncholinergic variant AChE-R, which increases in situations of stress and inflammation. That is why we think that AChE in EA undergoes a complex regulation at both molecular and post-translational level probably as a consequence of the physilogic role of each form of the enzyme. For this reason, this research project aims to analyse the molecular mechanisms that could affect the expression of HCA in AD, analysing in the brain of patients EA the methylation of the promoter of HAC and the levels of factors that control the splicing of the different variants. It will also analyse the levels of miR-132 that has been seen to regulate AChE and the regulation of its promoter as a trigger for its involvement in EA. In cell cultures we will analyse whether P-tau overexpression and Aß treatment affect the activity of the AChE promoter and splicing factors. On the other hand, the involvement in the process of glycosylation of the enzyme as responsible for the increase of inactive forms in EA will be investigated. To this end, the glycosylation of AChE in the brain of EA will be determined by interaction with lectins and the levels of glycosyltransfers involved, deepening the role of Aß in this alteration. We will also analyse the possible involvement of PS1 in its chaperone facet in AChE glycosylation. (English)
12 October 2021
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Elche/Elx
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Identifiers
PI17_00261
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