CORDIS
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Role of prolyl oligopeptidase in neuroinflammation and novel therapeutic use of specific POP inhibitors

Role of prolyl oligopeptidase in neuroinflammation and novel therapeutic use of specific POP inhibitors

Objective

Neurodegenerative diseases present a broad range of phenotypic symptoms derived from deterioration of different brain functions, such as controlling movements, processing information or memory. All those symptoms are caused by the loss of specific neurons controlling those processes. All neurodegenerative diseases result from damage of neurons or their myelin sheaths that eventually will lead to dysfunction and disabilities. The neuroinflammatory hypothesis of neurodegenerative diseases proposes that inflammation contributes to their pathogenesis. Recent studies have provided information of the direct role of prolyl oligopeptidse (POP) and its specific inhibitors in toxic neuroinflammatory responses, since has been observed that POP is 1) mediator of human microglial neurotoxicity, 2) it is involved in the production of chemoattractants and proinflammatory chemokines derived from collagen and 3) in vitro POP substrates ameliorates behavioural deficits in Alzheimer’s disease models by reducing neuroinflammatory responses. The project aims to contribute to the knowledge on the molecular mechanism involving POP and its inhibitors in the frame of inflammation and neurodegeneration, with the last objective of promoting therapeutic applicability of POP inhibitors. The proposal implementation will consider different approaches, such as clinical and biochemical and pharmacological studies in cell cultures and animal models. During the carry out of the project, we will measure POP activity and protein levels from patients suffering neurodegenerative diseases as well as we will evaluate the endogenous POP inhibitor. In addition, we will test the impact of POP inhibitors on induced neurotoxicity cell cultures and on the pathology progression of animal models. The proposal promises to generate applicable research, strengthen collaborative agreements and promote the convergence of efforts to increase the European competitiveness.
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Coordinator

HELSINGIN YLIOPISTO

Address

Yliopistonkatu 3
00014 Helsingin Yliopisto

Finland

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 178 088

Administrative Contact

Katariina Vainio-Mattila (Ms.)

Project information

Grant agreement ID: 254127

Status

Closed project

  • Start date

    1 March 2010

  • End date

    29 February 2012

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 178 088

  • EU contribution

    € 178 088

Coordinated by:

HELSINGIN YLIOPISTO

Finland