The National Institute on Aging considers Parkinson’s Disease (PD) is a brain disorder. Other descriptions characterize it as a progressive, neurodegenerative disorder. Scientists know there is a loss of brain cells that produce dopamine, which regulate one’s voluntary movements.

But there’s a disturbing limit to what we truly understand about this disorder. According to the NIA, “scientists still do not know what causes cells that produce dopamine to die.” One investigator with a research laboratory in the Van Andel Institute’s Department of Neurodegenerative Science wants to figure that out.

The lab, with its focus on PD, wants to know more about how cells and cell-to-cell communication in the brain are affected by Parkinson’s. The Chu Lab is on a mission to “identify mechanisms that contribute to progressive degeneration of midbrain dopaminergic neurons, and abnormal circuit activity that underlies the devastating motor symptoms of Parkinson’s disease.”

Even more ambitious, the goal is also to develop therapies that could modify the progression of the disease. They are looking at precision strategies, where they could target specific types of neurons or neural circuits to prevent and treat the disease.

The person behind this lab’s name is Van Andel Institute assistant professor Hong-yuan Chu. Chu received his Ph.D. in pharmacology from the Shanghai Institute of Materia Medica and did his postdoctoral training at the National Institute of Mental Health and Northwestern. In 2019, he joined Van Andel Institute’s Center for Neurodegenerative Science as an assistant professor.

Different behaviors

Specifically, Chu’s lab are analyzing the relationship between alpha-synuclein and the amygdala. Let’s break those complicated terms down.

Alpha-synuclein refers are abnormal proteins that have been linked to Parkinson’s disease . The biological function of alpha-synucleins are not fully understood, Chu says, and that abnormal aggregation that occurs “plays a mysterious role in why and how Parkinson’s disease arises.” The proteins are abundant in the brains, and smaller amounts can also be found in the hear, muscle, and other tissues.

The amygdala is a part of the brain that helps regulate emotions. This is where emotions are given meanings and associated to responses. There are two, one in each hemisphere or side of the brain.

“In our brain, there exists a network that controls our emotions and memories associated with emotion. For example, a flash of remembrance of previous holiday parties perhaps makes you feel happy, while recalling an attack by a poisonous snake provokes fearful feelings,” says Chu. He also reported a clinical observation: “…the amygdala shows high levels of alpha-synuclein clumps in people with Parkinson’s, and these people often experience different psychiatric symptoms, such as apathy, anxiety and depression-like behaviors.”

So the amygdala and these alpha-synuclein proteins seem to be connected somehow, and according to Chu, understanding this relationship is understanding “the very biology that underlies psychiatric symptoms in people with Parkinson’s.”

Hunting for the cause

Columbia University’s Department of Neurology has noted what scientists know and what they still do not know about PD, noting that there are a bunch of myths floating around Parkinson’s.

“It is a myth that Parkinson’s disease was cured after the introduction of levodopa (L-dopa) in the 1960s… With today’s medicine, we have yet to find a cure for Parkinson’s disease. However, based on the severity of the symptoms and medical profile, the doctor will establish an appropriate treatment protocol.”

Even though the specific cause of the disease is unknown, the CU department pointed out, medical experts believe the symptoms are related to a “chemical imbalance in the brain caused by brain-cell death.”

Is the environment a suspect in the cause of PD? It’s something worth considering.

“Environmental causes are being researched and the strong consistent findings are that rural living, exposure to well water, and exposure to agricultural pesticides and herbicides are related to PD,” said the CU department. “It is important to remember, however, that these factors do not guarantee the development of PD, nor does their absence prevent it.”

They went on to say that “Having one or more close relatives with PD increases one’s risk of developing the disease; however, unless there is a known genetic mutation for PD present, the increased risk is only 2 to 5 percent.”

All in all, researchers, they added, currently believe that in most the cause of PD is a combination of genetics and environmental exposure. Undoubtedly, we’ll learn more about this condition which affects 10 million people worldwide. For now, however, it’s proving a tough nut to crack.