Identifying a new drug target for the treatment of Alzheimer's disease
Lead Research Organisation:
University of Manchester
Department Name: School of Biological Sciences
Abstract
Inflammation contributes to the progression of Alzheimer's disease (AD) and on-going research is establishing the NLRP3-inflammasome complex as one of the most important regulators of inflammation in AD. The NLRP3 inflammasome forms a molecular platform inside microglial cells, catalysing the activation of the protease caspase-1. Caspase-1 is responsible for converting the potent pro-inflammatory cytokine interleukin-1beta (IL-1beta) from an inactive to an active secreted form, which is recognised as a major contributor to a number of diverse diseases and key therapeutic target. Active caspase-1 is present in the brains of humans with AD, suggesting that NLRP3 may contribute to the human condition. NLRP3 is also central to the development of inflammation, pathology and memory deficits in a mouse model of AD. Anti-IL-1 drugs, such as the biologicals canakinumab and anakinra, do not easily penetrate the brain and there are no molecules known to directly target NLRP3 in clinical use. We have identified the volume regulated anion channel (VRAC), a Cl- channel in the plasma membrane, as an important regulator of the NLRP3 inflammasome, and a potential target to limit NLRP3-dependent inflammation. Here we hypothesise that VRAC contributes to the inflammation that underpins the pathological process of AD and therefore aim to establish VRAC as a therapeutic target for AD.
Organisations
People |
ORCID iD |
Catherine Lawrence (Primary Supervisor) | |
James Cook (Student) |
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
MR/N013751/1 | 01/10/2016 | 30/09/2025 | |||
1916417 | Studentship | MR/N013751/1 | 01/10/2017 | 30/09/2021 | James Cook |
Description | ARUK Science Day |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | ARUK organised a science day at the museum of science and industry in manchester, as part of a larger event run by the museum, where our lab was involved in running several activities. Several hundred people attended the activities throughout the day. |
Year(s) Of Engagement Activity | 2019 |
Description | Big Brain 2018 School Engagement |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | The event was held at the University of Manchester and consisted of a number of small workshops delivering educational material relating to various aspects of neuroscience research happening at the university. This included research into Alzheimer's disease, which I and another PhD student delivered. 50-60 pupils attended, from various schools around Manchester. The pupils were interested in the material while at the event, though I don't personally know what other impacts the schools reported as I was not the primary organiser of the event. |
Year(s) Of Engagement Activity | 2018 |