A new Australian study modelling the early stages of Parkinson’s disease has given researchers insight into its causes and a possible treatment. “We’ve shown how inflammation within the brain is related to the development of Parkinson’s disease, and we’ve identified a potential mechanism that can prevent this inflammation,” says UNSW’s Dr Nic Dzamko.
“This is the result of four years’ worth of work, and we’re excited by the outcomes. It offers hope and introduces a new target for therapeutic research, which we’re now working on,” says Dr Dzamko, who is based at Neuroscience Research Australia (NeuRA).
Parkinson’s disease:
It is the 2nd most prevalent neurological condition after dementia. It is characterized by abnormal accumulation of a protein called alpha-synuclein and the loss of dopamine producing cells in a part of the brain-substantia nigra.
The loss of these cells causes trembling, stiffness, slowness of movement and loss of fine motor control. The research team used pluripotent stem cell technology to turn human skin cells into neuronal cells to understand the effects of brain inflammation.
The link between inflammation and Parkinson’s:
The brain uses toll-like receptors (TLR) to detect pathogens and regulate inflammation arising from compromised immunity. A consequence of activating TLR is the production of α-synuclein, which is responsible for creating ‘clumps’ of Lewy bodies; a hallmark of Parkinson’s disease.
“We found that a particular toll-like receptor, TLR2, is increased in neurons in post-mortem PD brain tissue, which provided new information for us. Given that neurons accumulate α-synuclein in Parkinson’s disease, our results suggest that TLR2 is of central importance in understanding how the disease starts.”
Using stem cells, researchers activated TLR2, which created an inflammatory response that increased the levels of α-synuclein, suggesting that inflammation is a cause, at least in part, of Parkinson’s disease.
The team also inhibited TLR2, which prevented the increase in alpha-synuclein ‘clumping’ in the stem-cell derived neurons, suggesting it is a target for further research into therapeutic interventions.
This could be used in human trials, in identifying a drug that can prevent TLR2-enabled increase in α-synuclein.