Aicee Calma was the recipient of the Parkinson's ACT George Webb Memorial Award in 2015. She undertook her clinical placement at the Montreal Neurological Institute/Hospital and wrote to Parkinson's ACT at the time to tell them all about her placement.
Today, Aicee continues her passion for neurology as a Junior Medical Officer at the Canberra Hospital and teaches at the ANU Medical School.
Letter from Aicee Calma to Parkinson's ACT, 2015
Greetings from Montreal Neurological Institute/Hospital!
On the first week of my neurology rotation at the Montreal Neurological Hospital, I had the pleasure of meeting one of the institute's top researchers in Parkinson’s, Dr Edward Fon.
Dr Fon has been working on Parkinson’s research for over 15 years now and has been running his laboratory in Montreal after finishing his Neurology Residency and Fellowship in San Francisco, California.
During his neurology residency, he developed an interest in the basic molecular biology of neurodegenerative diseases. From then, his interest has evolved to a number of projects centered on Parkinson’s.
The basic theme of his projects revolves around the molecular mechanisms that make dopaminergic neurons sensitive to degeneration. Up until recently, the only thing we knew about the molecular biology of Parkinson's was that it is caused by deposition of Lewy Bodies comprised of alpha synuclein proteins.
PINK 1 and Parkin
Dr Fon's latest main project looks at two other important proteins that may be linked to the pathophysiology of Parkinson's - namely PINK 1 and Parkin. In a nutshell, these two proteins are responsible for ensuring the quality of the neural mitochondria, or the powerhouse of the neurons (Narendra et al).
Dysfunctional mitochondria accumulate PINK1, which then recruits Parkin to promote 'tagging' of these mitochondria for destruction.
By looking at the genes that control expression of PINK1 and Parkin, we are beginning to understand the role of mitochondrial damage and oxidative stress to the neurons.
Dr Fon and his team have been looking at different structural configurations of Parkin.
Thus, understanding the structural basis of Parkin function will have huge implications for our capacity to regulate and manipulate its activity in PD.
With regards to the role of mitochondrial damage in Parkinson’s pathophysiology, a big question still remains though - and that is whether alpha synuclein deposition causes mitochondrial damage, or whether dysfunctional mitochondria leads to deposition of alpha synuclein in neurons.
Another part of Dr Fon's research focuses on the cell-to-cell transfer of alpha synuclein – a process that he described as 'seeding'.
Previous studies have shown that injection of defective alpha synuclein protein in healthy brain tissue can lead to aggregation of alpha synuclein years after the initial injection (Angot et al).
The proposed mechanism is through uptake of alpha synuclein by neurons.
Dr Fon and his team are currently looking at possible ways to block this mechanism - which could potentially be a way to effectively prevent onset of Parkinsonian symptoms.
Through a process called “High Throughput Screening”, they break down alpha synuclein into smaller oligomers and monomers of protein, label them with fluorescent tags, and place them in a series of test tubes containing various molecules and gene products.
Products that successfully bind to the alpha-synuclein monomers, may in the future have the potential to be developed into drugs which can hopefully be used to prevent onset of Parkinson’s.
Dr Fon has had a longstanding interest in discerning the molecular and cellular functions of Parkinson’s genes.
Although monogenic forms of Parkinson’s only make up a small proportion of cases, describing the molecular and cell biological mechanisms involved has become one of the most promising strategies for explaining the pathogenesis of the more common sporadic forms of Parkinson’s.