Genetics and Parkinson’s Disease – What’s the link?

Genetics and Parkinson’s Disease – What’s the link?

Genetics is increasingly becoming an important part of Parkinson’s disease. Especially in those patients who are diagnosed at a young age, genetics seems to play a big role. Researchers have identified a specific set of faulty genes that are either the actual cause of Parkinson’s or increase the chances of developing it.

Parkinson's disease genetics

Parkinson’s disease is caused by the death of certain cells in the brain that control movement. These cells are called dopaminergic neurons, and when they die, the brain becomes unable to release a neurotransmitter dopamine in sufficient amount. As a result, the body begins to show symptoms like tremor, stiffness, slow movement, and balance problem.

It is estimated that 15% of Parkinson’s cases are linked to genetics. Although the rest 85% cases appear with no apparent cause, researchers think that it mostly involved some genetic components.

The 1st genetic evidence of Parkinson’s disease

Earlier it was hard to believe that genetics could play a role in the development of Parkinson’s disease. Even though there were reports of positive family history in patients about a century ago. Still, it was a common realization that the disease has some unknown environmental factors and has nothing to do with genetics.

It was then in 1996 when researchers were able to find out an evidence of direct link between genetics and Parkinson’s disease. A gene called alpha-synuclein was identified as the cause of Parkinson’s in the population of Contursi kindred, a commune in the Campania region of south-western Italy. The gene has a key function in the brain cells and also linked to Alzheimer’s. It was found that the gene carries abnormal changes inside it that is responsible for the disease changes in the brain of patients.

(Genes carry abnormal changes which normally termed as mutation. Genes carrying mutation are usually passed from parents to their child and cause the disease in them. Sometimes, the disease appears in a person due to a mutation that is not being transferred from parents)

The identification of this gene was a breakthrough. It opened a new window of research opportunities for researchers in the field of Parkinson’s disease. More time and money were invested on the genetic aspect of the disease. And because of that, it didn’t take long to identify other genes that are linked to Parkinson’s.

Other genes linked to Parkinson’s disease

To date, more than 15 genes have been identified that are linked to Parkinson’s disease. Of these, 6 genes are those that are widely studied as they are directly involved in the disease development. These include SNCA, LRRK2, PRKN, PINK1, DJ-1, and ATP13A2.

(Genes exist in two copies, one from each parent. Parkinson’s disease may result from a mutation in a single copy of the gene, or it could be due to a mutation in both copies of the gene)

Mutation in the single copy of either SNCA or LRRK2 is sufficient to cause Parkinson’s disease. The person may get these mutated genes from one of his parents or it could be due to a complete new mutation.

Whereas, for the rest of the genes, a mutation in both copies is required to cause the disease in a person. In this case, a person surely gets a mutated gene from one of his parents. However, the parents usually do not show any sign of the disease in their life.

Now let’s have a brief look at each of these genes!

SNCA (alpha-synuclein)

This gene is primarily expressed in the brain where it performs many vital functions. Parkinson’s patients due to a mutation in this gene are rare and are under the age of 50s. Beside other typical symptoms, these patients show signs of dementia and learning problem.

In the early stage, drugs used against Parkinson’s (like L-Dopa) work efficiently to alleviate the effects of this gene. However, these effects reappear in the late stages.

LRRK2 (Leucine-rich repeat kinase)

This is one of the widely expressed genes in the body. Its expression controls many activities inside the cell. It makes connections with other genes and changes their functions according to cell status.

More than 100 mutations have been identified in the LRRK2 gene. The effects of mutation appear typically after the age of 50 and the patient usually shows postural instability and gait difficulty in the beginning. It is still not clear how mutation in this gene lead to these signs of the disease.

PRKN (Parkin)

This is probably the most extensively studied gene in Parkinson’s disease in the last decade. Although there are many functions that have been assigned to this gene, its main job is to take part in the process that removes unwanted proteins or other components from the cell.

People carrying a mutation in this gene can develop Parkinson’s usually before the age of 40, preferably in their mid-thirties. Some can develop it after 40. The progression of the disease is slow and the patient shows a good response to medication.

PINK-1 (PTEN-induced kinase-1)

PINK1 is a well-known gene that helps in protecting the cell from stressed conditions. Inside the cell, it is expressed in the mitochondria, also known as the powerhouse of the cell.

PINK1 has been shown to work together with the PRKN gene to ensure the normal production of energy in the cell. Inside the cell, they both make a pathway that helps to deal with damage caused by defects in mitochondria.

Parkinson’s patients carrying mutation in PINK1 are below the age of 40, although some can develop the disease after that.

PARK7 (Parkinson’s disease protein 7)

This is also known as DJ-1 (protein deglycase). It is expressed throughout the body and its main function is to protect the cell from oxidative stress insult.

It’s thought that PARK7 works in parallel to Parkin and Pink1 genes; together they form a complex to control the abnormal functions of mitochondria under stressed condition.

Mutation in PARK7 gene has been known to cause Parkinson’s at a young age. In most cases, the disease signs appear before the age of 45.

ATP13A2 (ATP (adenosine triphosphate)-ase cation transporting 13A2)

This newly discovered gene has shown to cause a rare form of Parkinson’s known as Kufor-Rakeb syndrome. It is expressed mainly in the brain where it protects brain cells from various types of insults.

Mutation in ATP13A2 gene can strike with disease signs at a very young age. The youngest patient reported to carry a mutation in ATP13A2 was a 12 years old Lithuanian boy. People who are affected by its mutation also show dementia problem.

To summarize

It is now widely accepted that genetics plays an important role in the development of Parkinson’s disease. Several genes have been identified that, when mutated, are known to cause the disease in people younger than 50 years of age. Researchers believe that unravel the mechanism of these genes and the identification of new genes would help us to better understand the nature of Parkinson’s disease. It will also help in developing new therapies for the disease.

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