Parkinson’s disease (PD) results from the progressive loss of specific brain cells responsible for movement. As these neurons deteriorate, patients experience tremors and difficulty with balance and coordination. Although treatments can alleviate specific symptoms, nothing slows the progression of the disease. Projections estimate that by 2031, approximately 163,000 Canadians will be living with Parkinson’s, emphasizing the necessity of effective therapeutic options. 

PD is often associated with aging, as most patients are diagnosed after the age of 60. However, some patients develop symptoms decades earlier. Early-onset Parkinson’s—which develops before age 50—puts patients at a particular disadvantage because they live with the disease for longer and consequently face limitations during important stages of adulthood, often experiencing heavier emotional and economic burdens.

Sabrina Romanelli, a third-year PhD student in Pharmacology at McGill, is currently working in the Trempe Lab to better understand the molecular factors that drive this form of Parkinson’s.

“I really wanted to work in PD research because my grandmother had the disease [….] I saw her go through it, and I understood the toll that it takes on people, and the way that people suffer with the disorder,” Romanelli said in an interview with The Tribune.

The Trempe Lab concentrates on early-onset Parkinson’s by studying two proteins: PINK1 and Parkin. These proteins maintain the health of the mitochondria. Under normal conditions, the mitochondria powers cellular functions; however, when mitochondria become damaged, they generate harmful by-products that can cause neuron death. PINK1 detects the damage, stabilizes on the surface of defective mitochondria, and signals that it must be eliminated. Parkin then follows this signal and clears the defective mitochondria. Mutations in either PINK1 or Parkin disrupt this process, preluding to early-onset Parkinson’s.

McGill researchers are particularly interested in how PINK1 stabilizes on damaged mitochondria long enough to activate Parkin. The TOM complex, a protein structure responsible for transporting proteins into mitochondria, is at the heart of this process. One of its subunits, TOM7, may help hold PINK1 in place when mitochondria are damaged; in the absence of TOM7, PINK1 fails to function.

“I’m trying to better understand how PINK1 is able to interact with this complex,” Romanelli said. “And the reason why this is so important is because the PINK1-TOM complex has become this key therapeutic target for Parkinson’s disease.”

The Trempe Lab currently studies how TOM7 influences PINK1’s behaviour to determine how this subunit affects PINK1 stabilization.

“One thing that I’m doing is taking wild type cells and cells that have TOM7 not present and running that on mass spectrometry to see if there’s any key differences between the conference composition of the cells,” Romanelli explained.

Studying PINK1 is challenging because the protein is unstable under normal conditions. Cells rapidly degrade it when mitochondria are functioning normally. As a result, experiments require timing and careful manipulation of mammalian cells, which can be unpredictable and sensitive to their environment. Despite this, mammalian cell systems are essential for Parkinson’s research because they are comparable to the characteristics of human neurons.

“I think it’s an important field to study primarily because […] as the population keeps aging, we are going to see more people being diagnosed with neurodegenerative diseases,” she said. “But I think what’s really good about our lab is the fact that we’re focusing on early-onset Parkinson’s, […] because these people have to suffer with the disease for longer periods of time.” 

Studying the interactions between PINK1 and the TOM complex has important implications for future therapies. The PINK1-TOM7 connection is a promising therapeutic target, and drug candidates may already be affecting this pathway. However, without a good understanding of how PINK1 stabilizes on mitochondria and initiates the removal of damaged components, drug design remains challenging. Understanding this mechanism could allow for the development of treatments that act preventively rather than mitigating existing symptoms.

“What I would want people to take away is the fact that basic research could be very powerful. It starts at the lab bench,” Romanelli said. “I won’t find a cure in my PhD, but hopefully my PhD will bring us a step closer to a cure.”