Tag Archives: alpha-synuclein

Parkinson’s Disease: mystery solved by a protein?

Source: Army US

Parkinson’s disease is a lifelong disease with no cure. According to this website, out of all the diseases associated with the brain, Parkinson’s is the second most common. Parkinson’s is characterized by problems with movement, such as uncontrollable shaking and difficulty walking.

Unexplained Cell Death is the cause of Parkinson’s Disease

On a cellular level, Parkinson’s is the result of nerve cell death. Neurons are the cells that make up our nervous system. Since the nervous system is responsible for our ability to think, feel and move, neurons are pretty important. Especially, since, after a certain age, we stop producing new neurons.

Essentially, Parkinson’s Disease is caused by the massacre of these precious neurons. Specifically, Parkinson’s is caused by the nerve cell death in a specific part of the brain,  the Substantia Nigra. Nerve cells in this region produce dopamine, a chemical signal involved in producing movement.

As of now, we have yet to find a clear culprit responsible for the cell death in Parkinson’s. However, active research has shed some light on the matter.

Relative location of the Substantia Nigra. Source: Wikimedia Commons

Lewy Bodies’ association with Parkinson’s Disease

Lewy bodies are essentially clumps of broken protein, of different types and sizes. According to this study, Lewy bodies are especially common in the dopamine-producing cells belonging to patients with Parkinson’s. Because they have such a strong association with the disease, Lewy Bodies and their protein contents have piqued scientists’ interests.

One protein of note, is alpha-synuclein. In the healthy body, the function of this protein is unknown. In diseased state, however, scientists have found they make up a large portion of Lewy Bodies. With this, we turn to another study that investigated alpha-synuclein’s role in hereditary Parkinson’s Disease.

Example of a Lewy Body (the dark red circle). Source: Wikimedia Commons

Alpha-Synuclein’s role in Hereditary Parkinson’s

There are two broad categories of Parkinson’s: hereditary and non-hereditary. The hereditary type is rare and, like most hereditary disease, the cause can be found in the patient’s genes. Specifically, researchers have found a mutation in the gene that codes for alpha-synuclein. The mutation ended up producing proteins with the wrong shape. The correct proteins should have what is called an alpha helix shape; meanwhile, the defective protein had a beta sheet shape instead (refer to diagram below). Unlike alpha helices, beta sheets have the ability to stack on top of each other to form an amyloid fibril. These structures start to pose a problem because they are hard to degrade and are useless, just hanging around inside the cell. Amyloid fibrils have the potential to kill neurons and explains the cell death seen in this particular type of Parkinson’s.

The researchers for this study feel that the same mutation is probably no the cause for the more common, non-hereditary version of this disease. However, they also feel that a similar process may be at play here and their findings have provided groundwork for future research.