Title of project or programme

In vivo models of disease and toxicity in the nervous system

Principal Investigators of project/programme grant
Title Forname Surname Institution Country
Professor Giovanna Mallucci MRC Toxicology Unit UK
Address of institution of lead PI
Institution MRC Toxicology Unit
Street Address Hodgkin Building, PO Box 138, University of Leicester, Lancaster Road
City Leicester
Postcode LE1 9HN
Country
  • United Kingdom
Source of funding information

Medical Research Council

Total sum awarded (Euro)

1673056.14

Start date of award

01-04-2008

Total duration of award in months

24

The project/programme is most relevant to
  • Prion disease
  • Neurodegenerative disease in general
Keywords
Research abstract in English

Neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s disease and amyotrophic lateral sclerosis, have enormous clinical and economic impact world wide. Irrespective of the final pattern of clinical symptoms, they all are caused by an irreversible loss of neurons, which cannot be cured. But before neuronal death, there are neuronal dysfunction and synaptic impairment, which potentially can be treated.

My background is in prion diseases, modelling these in transgenic mice to look at mechanisms of neurotoxicity and developing new therapeutic approaches. In particular, I focused on the changes of early prion neurotoxicity and recovery from it. This new programme uses mouse models to understand the early molecular events in prion and other neurodegenerative diseases, looking in parallel at potential therapeutic targets for prevention of neuronal dysfunction and death.

Our main aims are to:

1. Characterise pre-degenerative neuronal changes.

2. Understand what triggers ultimate commitment to death in a malfunctioning neuron.

3. Define the molecular targets and the temporal window for functional recovery.

Initially, these questions will be addressed using our established mouse model of prion disease where early pathology is associated with a pivotal point in neuronal survival/death, and there is potential for recovery. We will use molecular biological, biochemical and neurophysiological techniques, as well as neuronal imaging in culture and in vivo to characterise the underlying cellular and synaptic changes, including alterations in signalling pathways and ion channels.

The broader aims of the programme are:

4. to generate new mouse models to look at individual pathways implicated in early dysfunction and their effect on neuronal function and death.

5. to address therapeutic strategies for the treatment of neurodegeneration.

Lay Summary

    Principal Investigators

    Professor G Mallucci

    Institution

    MRC Toxicology Unit

    Contact information of lead PI

    Country

    United Kingdom

    Title of project or programme

    In vivo models of disease and toxicity in the nervous system

    Source of funding information

    MRC

    Total sum awarded (Euro)

    € 9,477,939

    Start date of award

    01/09/2011

    Total duration of award in years

    5.0

    The project/programme is most relevant to:

    Prion disease | Neurodegnerative disease in general

    Keywords

    Research Abstract

    Neurodegenerative diseases, such as Alzheimers, Parkinsons, Huntingtons disease and amyotrophic lateral sclerosis, have enormous clinical and economic impact world wide. Irrespective of the final pattern of clinical symptoms, they all are caused by an irreversible loss of neurons, which cannot be cured. But before neuronal death, there are neuronal dysfunction and synaptic impairment, which potentially can be treated.||my background is in prion diseases, modelling these in transgenic mice to look at mechanisms of neurotoxicity and developing new therapeutic approaches. In particular, I focused on the changes of early prion neurotoxicity and recovery from it. This new programme uses mouse models to understand the early molecular events in prion and other neurodegenerative diseases, looking in parallel at potential therapeutic targets for prevention of neuronal dysfunction and death.||Our main aims are to:|1. Characterise pre-degenerative neuronal changes.|2. Understand what triggers ultimate commitment to death in a malfunctioning neuron.|3. Define the molecular targets and the temporal window for functional recovery.||Initially, these questions will be addressed using our established mouse model of prion disease where early pathology is associated with a pivotal point in neuronal survival/death, and there is potential for recovery. We will use molecular biological, biochemical and neurophysiological techniques, as well as neuronal imaging in culture and in vivo to characterise the underlying cellular and synaptic changes, including alterations in signalling pathways and ion channels.||The broader aims of the programme are:|4. to generate new mouse models to look at individual pathways implicated in early dysfunction and their effect on neuronal function and death.|5. to address therapeutic strategies for the treatment of neurodegeneration.

    Lay Summary

    One of the greatest challenges in neuroscience, and to public health, is how to treat neurodegenerative diseases. These diseases involve the death of brain cells. When they are lost, the functions they control memory, movement and emotion are also irreversibly lost. In order to treat these disorders, we need to understand why brain cells degenerate and die. Most importantly, we need to understand the earliest stages of this process as this gives us the greatest chance of intervening to prevent cell death. I previously made a mouse model of prion disease in which early degeneration is reversible. In these mice, early structural changes in brain cells lead to changes in behaviour, memory and electrical signalling, very like early changes seen in human neurodegenerative disorders. Using either special genetic techniques we were able to reverse this process. The structural, behavioural and memory changes were all reversed and instead of dying, the mice recovered and lived a normal lifespan. We aim to understand the processes that control this recovery and use this to find targets for treating neurodegeneration.

    Further information available at:

Types: Investments > €500k
Member States: United Kingdom
Diseases: Neurodegenerative disease in general, Prion disease
Years: 2011
Database Categories: N/A
Database Tags: N/A

Export as PDF