Professor David AllsopProfessor
I am interested in the pathological role of misfolded 'amyloid' proteins in a range of different human diseases, including some important neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, and also Type 2 diabetes.
My research is concerned with the devopment of peptide-based inhibitors of amyloid aggregation as a novel approach to treatment of these diseases, and on the development of new blood-based biomarkers for improved early diagnosis. I am also interested in the interaction between amyloid proteins and redox-active metal ions, and the role that this might play in tissue damage.
My research is supported by the Defying Dementia campaign (http://www.lancaster.ac.uk/defyingdementia/)
Projects in my laboratory include:
- Development of retro-inverted peptides and liposome-peptides as β-amyloid and tau aggregation inhibitors, for the treatment of Alzheimer's disease. These inhibitors are designed to block the formation of senile plaques and neurofibrillary tangles in the brain. In collaboration with MAC PLC we are planning to get these inhibitors into human clinical trials.
- Development of peptide-based inhibitors of amylin aggregation for the treatment of Type 2 diabetes. Amyloid fibrils composed of amylin accumulate in the pancreas in Type 2 diabetes, and cause the degeneration of islet cells and loss of insulin section. Blocking amylin aggregation could provide a novel treatment for this form of diabetes.
- Development of biomarkers in blood for the early diagnosis of neurodegenerative diseases. Our recent research has shown that levels of phosphorylated tau are elevated in blood plasma from patients with Alzheimer's disease (collaboration with a group in Kyoto, Japan), and that 'biospectroscopy' can be used to differentiate between Alzheimer's disease and other forms of dementia (collaboration with scientists at UCLAN).
- Recent research in collaboration with Professor Barbara Maher (LEC) has identified, for the first time, the presence of pollution-derived magnetite nanoparticles in the human brain. We are now investigating the toxic effects of these iron particles on cultured brain cells, and determining if their presence and distribution in the brain correlates with Alzheimer-type pathology.
The formation of fibrillar aggregates is a common feature of numerous different 'protein conformational' diseases. In these diseases, normally soluble proteins are deposited in the form of insoluble fibrils inside and/or outside of cells. Extracellular fibrillar deposits (often called 'amyloid') can be found in many different tissues and organs throughout the body. Localised deposits are found in some diseases, such as Type 2 diabetes, where they are restricted to the pancreas, and some important neurodegenerative diseases, where they are found in the brain and central nervous system. My research is concerned with the pathological role of these misfolded proteins.
There are three major aspects to my research:
1. Mechanism of amyloid toxicity
We are studying the potential mechanisms by which the accumulation of protein aggregates can lead to cellular degeneration and loss and have discovered that the aggregating proteins implicated in Alzheimer's disease, Parkinson's disease, prion disease and Type 2 diabetes all have the common ability to generate hydrogen peroxide. They do this through key interactions with redox-active transition metal ions, particularly iron and copper ions. Our hypothesis is that tissue damage caused by the formation of 'reactive oxygen species' could be a common mechanism of cell damage in several different protein misfolding disorders. This also ties in to our recent studies on brain magnetite.
2. Disease-linked proteins as potential biomarkers
A further aspect of our research is the detection of proteins implicated in the pathogenesis of neurodegenerative disease as potential biomarkers in blood. There are two main aspects to this work:
- The development of improved diagnostic markers, to allow early detection and consequently improved treatment of disease.
- The development of molecular markers to enable the tracking of disease progression in already diagnosed patients - this would help to streamline drug testing in clinical trials.
Recently, we carried out the first longitudinal study on α-synuclein as a biomarker for Parkinson's disease (supported by MRC) and are developing other blood-based markers for Alzheimer's disease.
3. Amyloid inhibitors as novel therapeutics
Blocking the formation of early toxic protein aggregates could be a novel approach to the treatment of protein misfolding diseases. We have recently developed retro-inverted peptide aggregation inhibitors that could provide a new treatment for Alzheimer's disease, and are following a similar strategy for late-onset diabetes. We have also found that the potency of these inhibitors can be greatly improved by attaching them to nanoparticles.
Our Research has been supported by grants from Medical Research Council, Engineering and Physical Sciences Research Council, European Union, The Wellcome Trust, Alzheimer's Society, Alzheimer's Research UK and The Sir John Fisher Foundation.
Total grant income over the last ten years has exceeded £2.4 million.
BIOL111: MOLECULES OF LIFE, 2 workshops on molecular structure and protein purification
BIOL125: HUMAN PHYSIOLOGY (Module Organiser), 12 lectures on the nervous system, cardiovascular system, lungs and respiration, and the digestive system; 8 practical classes/workshops
BIOL354: PATHOBIOLOGY (Module Organiser), 3 lectures on brain diseases; 5 practicals/workshops
BIOL364: AGEING, 1 lecture on the ageing brain
BIOL436: BRAIN DISEASES, 1 lecture on Alzheimer's disease
- Member of Research Executive Committee, The Alzheimer's Society (2007-2017)
PhD Supervision Interests
PhD projects are available in all of the research areas described above.
Retro-inverso peptide inhibitor nanoparticles as potent inhibitors of aggregation of the Alzheimer’s Aβ peptide
Gregori, M., Taylor, M.N., Salvati, E., Re, F., Mancini, S., Balducci, C., Forloni, G., Zambelli, V., Sesana, S., Michael, M., Michail, C., Kolosov, O.V., Tinker-Mill, C.L., Sherer, M., Harris, S., Fullwood, N.J., Masserini, M., Allsop, D. 02/2017 In: Nanomedicine: Nanotechnology, Biology, and Medicine. 13, 2, p. 723-732. 10 p.
Magnetite pollution nanoparticles in the human brain
Maher, B.A., Ahmed, I., Karloukovski, V.V., MacLaren, D., Foulds, P., Allsop, D., Mann, D., Torres-Jardon, R., Calderon-Garciduenas, L. 27/09/2016 In: Proceedings of the National Academy of Sciences. 113, 39, p. 10797-10801. 5 p.
Alzheimer's Research Project - Years 11,12 & 13
01/10/2019 → 30/09/2022
Alzheimer's Research Project - Year 10
01/10/2018 → 30/09/2019
Defying Dementia: Preliminary studies into peptide-based inhibitors of Tau aggregation
01/07/2018 → 31/12/2018
UHMBT Studentship: Cognitive Dysfunction and Early Dementia in Chronic Kidney Disease
01/10/2014 → 30/09/2015
Towards disease diagnosis through spectrochemical imagining of tissue architecture
12/11/2013 → 11/11/2016
Novel biomarkers and alzheimer's disease
01/10/2009 → 30/09/2013