Name of Fellow

    Jill Fowler



    Alzheimer's Research UK

    Contact information of fellow


    United Kingdom

    Title of project/programme

    Therapeutic potential of boosting astrocytic Nrf2-mediated antioxidant signalling in combating white matter damage, amyloid pathology and cognitive deficits caused by chronic cerebral hypoperfusion

    Source of funding information

    Alzheimer's Research UK

    Total sum awarded (Euro)

    € 319,950

    Start date of award


    Total duration of award in years


    The project/programme is most relevant to:

    Alzheimer's disease & other dementias


    Cell Death | Oxidative Stress

    Research Abstract

    Prolonged modest reductions in blood supply to the brain (chronic hypoperfusion) are an early feature of Alzheimer’s disease (AD).  There is evidence, including our work, that sustained hypoperfusion leads to over-production of harmful molecules (free radicals) causing cell damage through oxidative stress.  This leads to increased production of amyloid, a key molecule implicated in AD. In normal healthy brain, there are defence mechanisms (anti-oxidant) to prevent damage to brain cells.  In particular a new molecule has been discovered called Nrf2, which can switch on several antioxidant molecules and exert protection.  This project will test the hypothesis that hypoperfusion leads to increased oxidative stress, amyloid production and brain damage associated with impaired cognition which can be ameliorated by boosting the anti-oxidant capacity of the brain through targeting Nrf2.  Using experimental model systems, we will firstly determine the effects of hypoperfusion or increased amyloid on Nrf2 related signalling pathways, the extent of oxidative damage and whether this is exacerbated when levels of Nrf2 are reduced. Central to this proposal we will address whether boosting anti-oxidant mechanisms either by drugs, or by using  specialised genetically modified mice in which anti-oxidant capacity is enhanced, can protect against the effects of hypoperfusion and amyloid.

Types: Fellowships
Member States: United Kingdom
Diseases: Alzheimer's disease & other dementias
Years: 2016
Database Categories: N/A
Database Tags: N/A

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