In a world first, Australian researchers have discovered a new mechanism in the brain that has the potential to reduce the impact of debilitating neuroinflammatory diseases.
Australian researchers have discovered a new mechanism in the brain that has the potential to reduce the impact of debilitating neuroinflammatory diseases such as Alzheimer’s disease, multiple sclerosis and motor neuron disease.
Findings of the study were published in the Molecular Neurobiology Journal.
A team of researchers from UNSW Sydney’s Centre for Healthy Brain Ageing (CHeBA), Macquarie University’s Neurodegenerative Diseases Research Centre and the Peter Duncan Neurosciences Unit, St Vincent’s Hospital, has identified a new process for the uptake of the neurotoxin quinolinic acid (QUIN) in human neurons that could reduce the impact of major inflammatory diseases.
The study is a world first in characterising a mechanism for QUIN uptake into primary human neurons via a transporter called EAAT3.
"Our research is significant as it opens new potential targets for reducing neuroinflammatory disorders that have been induced by toxins from the build-up of QUIN in the brain, said Dr Nady Braidy," Lead author and Leader of CHeBA’s Brain Ageing Research Laboratory.
“We have previously demonstrated that disruption in the kynurenine pathway and over-production of QUIN have been associated with a large number of infectious and neurological diseases, including AIDS-related dementia complex, motor neuron disease, Huntington’s disease, Alzheimer’s disease and multiple sclerosis,” said Professor Gilles Guillemin (Macquarie University).
The latest study builds on previous research by Prof Guillemin who demonstrated that in Alzheimer’s disease and motor neuron disease (MND), excessive amounts of QUIN accumulate within the human brain and in neurons and motor neurons.
According to Dr Braidy, as an example, the pathobiology of Alzheimer’s disease is complex, with a variety of toxins likely to contribute. Professor Brew (St Vincent’s Centre for Applied Medical Research) added: “Nonetheless, the increased QUIN-related activity of EAAT3 is likely to compromise its ability to ‘dispose’ of other toxins that are also related to Alzheimer’s disease.”
Given the importance of EAAT3 in neuronal QUIN uptake and the excitotoxic potential of QUIN accumulation in the brain, pharmacological modulation of EAAT3 is of major significance for the treatment of Alzheimer’s disease and other neurodegenerative diseases associated with pathologically elevated levels of exogenous QUIN.
“Specific drugs targeting EAAT3, and alternative strategies to modulate EAAT3 function are necessary to provide renewed insights on the function and clinical relevance of EAAT3 in normal brain health and neurodegenerative disorders, including Alzheimer’s disease,” said Dr Braidy.
The research was a collaboration between researchers at the Centre for Healthy Brain Ageing (CHeBA), UNSW Sydney, Peter Duncan Neurosciences Unit St Vincent’s Centre for Applied Medical Research, Monash University, and Macquarie University.