The Amyloid-Binding Compound Research Group 

The Amyloid-Binding Compound Research Group has been led by Dr Nat Milton since September 1996 and is currently based in Leeds.  Amyloid fibrils are implicated in many disorders including Alzheimer's disease, Parkinson's disease, Type II Diabetes mellitus, Familial British Dementia, Familial Danish Dementia and Creutzfeldt-Jakob disease. The group has focused on the identification and characterization of endogenous amyloid-binding compounds.

The kisspeptin peptide colocalizes with the amyloid-ß peptide in the pons region of the brain in Alzheimer's disease (Chilumuri et al 2013). The Amyloid-Binding Compound Research Group identified the kissorphin peptide, a novel NPFF-like derivative of kisspeptin (Milton 2012; Gibula-Bruzda et al 2017). Kissorphin shows binding to the Alzheimer's associated amyloid-ß peptide plus amylin and prion protein fragments (Milton et al 2012). Models of KiSS-1 overexpression have been characterized (Chilumuri & Milton 2013) and protect against amyloid toxicity. Other groups have confirmed the utility of kisspeptin (Jiang et al 2015) for prevention of amyloid-ß toxicity in vivo and the potential for therapeutic use in Alzheimer's disease. 

A UK patent for the use of kissorphin peptides in the treatment of Alzheimer's disease, Creutzfeldt jakob disease and diabetes mellitus (Milton 2017) has been granted.

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Amyloid-Binding Compound Research Group discoveries include Amyloid peptide interactions with catalase (Chilumuri et al 2013Milton & Harris 2014), kisspeptin peptides (Milton et al 2012) plus a phosphorylated derivative of amyloid-ß (Milton 2001) and cannabinoid neuroprotection against amyloid-ß (Milton 2002). Other groups have confirmed the utility of catalase (Nell et al 2016) for prevention of amyloid-ß toxicity in vivo and potential for therapeutic use in Alzheimer's disease. The ser26 phosphorylated amyloid-ß has been found in Alzheimer’s disease brains, shows greater toxicity plus less aggregation (Milton 2001Milton 2005) and its presence has been confirmed by others (Kumar et al 2016). The discovery of cannabinoid neuroprotection against amyloid-ß (Milton 2002) has been confirmed in vivo (Aso & Ferrer 2014) and shows potential for development of cannabinoid agonists for therapeutic use in Alzheimer's disease. Recent studies by the Amyloid-Binding Compound Research Group have demonstrated neuroprotective actions of peptide cannabinoids in vitro (Werner et al 2017; Werner et al 2018). A full list of publications from the Amyloid-Binding Compound Research Group is included in the Publications page.

We have also identified fibril formation conditions for the non-amyloidogenic rat amylin peptide (Milton & Harris 2013), which have been used to screen for novel amyloid-binding compounds. Using this screening the group has identified a number of amyloid-binding compounds including the R9 peptide, kisspeptin and kissorphin.