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Regulation of cellular proliferation in chronic neurodegenerative disease: Microglial proliferation and neurogenesis in prion disease

Objetivo

An important aspect of chronic neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s or prion disease, is the generation of an innate inflammatory reaction within the central nervous system. Microglial cells play a leading role in the development and maintenance of this inflammatory reaction, showing enhanced proliferation and morphological activation. Moreover, during neurodegeneration and inflammation, the mechanisms that control neural stem cell biology are altered and may also affect disease progression, causing impaired neural stem cell renewal, migration and differentiation. Since these proliferative responses are both involved in neurodegeneration they may share common or perhaps antagonistic regulatory pathways.
In this project, using a tractable laboratory model of neurodegeneration (murine prion disease), we will study the time-course and molecular regulation of microglial and neural stem cell proliferative responses. Moreover, we will analyze the role of the inflammatory milieu in the regulation of the proliferative responses, in order to throw light on the progression of chronic neurodegeneration. These objectives will be addressed using a multidisciplinary technical approach, combining the use of transgenic animal models with cell culture systems, analyzed by cellular and molecular biology techniques. Furthermore, we will cross-validate our studies with the analysis of the microglial and neural stem cell proliferative responses in post-mortem brain samples from Alzheimer’s disease patients. This powerful combined approach would permit us to obtain results that will contribute to the understanding of mechanisms that drive progression of chronic neurodegeneration.

Convocatoria de propuestas

FP7-PEOPLE-2010-IEF
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Coordinador

UNIVERSITY OF SOUTHAMPTON
Aportación de la UE
€ 200 549,60
Dirección
Highfield
SO17 1BJ Southampton
Reino Unido

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Región
South East (England) Hampshire and Isle of Wight Southampton
Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Simon Mason (Mr.)
Enlaces
Coste total
Sin datos