Controlling neuro-inflammation in Alzheimer's disease
By 2050 a million Australians are estimated to be diagnosed with Alzheimer’s disease, the most common neurodegenerative disorder worldwide. Current therapeutic strategies, although initially promising, have been ineffective in treating disease progression. The laboratory which Mr Minter is apart of focuses on neuro-inflammation, an aspect common to all Alzheimer’s sufferers but not yet targeted therapeutically. He has identified a critical novel regulator of this neuro-inflammation termed the type-1 interferons and we are investigating how they contribute to Alzheimer’s disease progression. He has detected significant elevations of type-1 interferon in human brains from patients who have died from Alzheimer’s disease and also in animal models of Alzheimer’s disease. In cell culture, neurons that have no type-1 interferon are protected against amyloid-beta, a key toxic protein which triggers neuronal death in Alzheimer’s disease. Other cells in the brain, termed glial cells, are also key players in neuro-inflammation. In healthy people these cells help keep neurons functioning and remove any unwanted or damaged tissue from the brain. In Alzheimer’s disease these cells can become hyper-active and damage healthy neurons, worsening disease progression. He has identified that type-1 interferons are important in controlling these events in glial cell culture and are currently investigating this finding further. He proposes that therapeutic targeting of neuro-inflammation in Alzheimer’s disease remains an unrecognised means of combating disease progression. Specifically, therapeutics targeting type-1 interferons or other related mediators may prove beneficial in treating the neurodegenerative disorder.
Myles Robert Minter, Bevan Scott Main, Kate Maree Brody, Moses Zhang, Juliet Marie Taylor* and Peter John Crack* Soluble amyloid triggers a myeloid differentiation factor 88 and interferon regulatory factor 7 dependent neuronal type-1 interferon response in vitro Journal of Neuroinflammation 2015, 12:71
Minter MR*, Taylor JM*, Newman AG, Zhang M, Adlard PA, Crack PJ: Type-1 interferon signaling mediates neuro-inflammatory events in models of Alzheimer's disease. Neurobiol Aging 2013. DOI: 10.1016/j.neurobiolaging.2013.10.089 (*co-authored with Taylor JM)
Fon D, Zhou K, Ercole F, Fehr F, Marchesan S, Minter MR, Crack PJ, Finkelstein DI, Forsythe JS: Nanofibrous scaffolds releasing a small molecule BDNF-mimetic for the re-direction of endogenous neuroblast migration in the brain. Biomaterials 2013. DOI: 10.1016/j.biomaterials.2013.12.016 (collaborative work with broad implications to possible Alzheimer’s therapy by repopulating neurodegenerative areas)
Minter MR, Taylor JM, Zhang M, Newman AG, Adlard PA, Crack PJ: Type-1 interferons propagate neuro-inflammatory cascades in models of Alzheimer’s disease. Australian Neuroscience Society (ANS) and Dementia Ageing and Neurodegenerative DISeases group (DANDIS), Melbourne, VIC – Poster presentation.
Minter MR, Taylor JM, Zhang M, Adlard PA, Crack PJ: Amyloid-beta drives a type-1 interferon mediated neuro-inflammatory response in Alzheimer’s disease. Molecular Neurodegeneration, Cannes, FR – Poster presentation. Awarded the competitive BrightFocus international travel bursary based on submitted abstract. Abstract published online: Molecular Neurodegeneration. 2013. Vol 8 Issue Suppl 1. DOI: 10.1186/1750-1326-8-S1-P29.
Minter MR, Taylor JM, Main BS, Zhang M, Crack PJ: The neuronal type-1 interferon response to amyloid-beta is toll-like receptor-mediated. Students of Brain Research (SOBR) brain symposium, Melbourne, VIC – Poster presentation. Awarded 2nd place prize for best PhD student poster presentation.
Minter MR, Taylor JM, Main BS, Zhang M, Adlard PA, Crack PJ: Type-1 interferons modulate the glial phenotype in response to amyloid beta. Australian Society for Medical Research (ASMR) national scientific conference on ageing, Ballarat, VIC - Oral presentation. Received the Campion-Ma-Playoust memorial award for best young investigator oral presentation.
Minter MR, Taylor JM, Main BS, Zhang M, Crack PJ: Toll-like receptor detection of amyloid-beta triggers a type-1 interferon driven inflammatory response. St Vincent’s BiomedLink, Melbourne, VIC – Poster presentation.
Mr Minter has also written an article for the Dementia News blog.
Mr Minter submitted his PhD in mid-2015 and is about to start a post doctoral fellowship at the University of Chicago.