What happens in Parkinson’s disease, exactly?

What is it?

Parkinson’s disease, PD, is a neurodegenerative disorder that mainly affects the motor system (the neurons in the brain and spine that control movement). Typical symptoms include tremor, muscle stiffness, and slow movements. Many people with PD also experience neuropsychiatric symptoms, such as depression, dementia, and problems with cognitive tasks like planning and remembering.

PD is relatively common. It often has a late onset, and about 1% of people over 60 years old suffer from it.

The fact that PD is a neurodegenerative disorder means that it gets worse over time. With treatment many people can, however, continue leading quite independent lives for as much as 15 years after diagnosis. PD usually begins with motor symptoms that progress aggressively at first but more slowly later, and in the final stages of the disease, the neuropsychiatric problems become more frequent.

What causes it?

With the odd exception of a known genetic cause, in most cases of PD it is not known why the disease came about.

Head injuries and exposure to pesticides have been associated with higher levels of PD while, quite surprisingly, smoking and caffeine consumption seem to lower the risk.

What happens during it?

There is a small part in the middle of the brain called pars compacta. It doesn’t directly cause movement, but is plays an important role in the regulation of it. Pars compacta is where the largest brain damage occurs in PD. By the time the person has died, 70% of these cells can have died too.

Neurons need neurotransmitters in order to communicate with each other. Neurons act as pathways for electrical impulses. The first neuron releases neurotransmitters so that they bind to another neuron, and if there’s enough of the transmitter molecules, the impulse continues in the second neuron. Dopamine is one of these neurotransmitters, and the neurons in the pars compacta produce it. When these cells die in PD, the messages can’t get through in the way they should. With less and less dopamine, the person is less and less able to control the functions of any dopamine-dependent networks. Dopamine is widely used around the brain, which is why PD can also have a quite wide range of manifestations. It is thought, for example, that the brain continuously inhibits muscles from contracting. When a movement should be made, dopamine is released so that the inhibition of this particular motor system is removed, and it becomes free for activation. The lower levels of dopamine in PD leads the brain having to put more time and effort into overcoming the inhibition.

Our cells use glucose as energy, but they first need to transform the energy into a form they can use. That’s what mitochondria, little “cell-organs”, do. Alpha-synuclein is a protein found commonly in the brain, and it can be present in various different forms. It has recently been found that the accumulation of certain forms of alpha-synuclein in neurons is a key factor in the cell deaths associated with PD. The protein binds to another protein in mitochondria called TOM20. This isn’t good: the mitochondria can’t produce energy nearly as efficiently as they used to. On top of that, they start producing very reactive substances – and these substances damage the cell, as they will react with practically anything on their way, breaking the existing chemical structures.

How can it be treated? 

There is currently no cure for PD. Treatment consists of relieving the symptoms (which can immensely improve the quality of life of the patient), instead of halting or reversing the cell deaths.

Levodopa is a medication which is eventually used by almost all PD patients. It is turned into dopamine inside the brain, which obviously helps with the symptoms, as they are caused by a lack of dopamine. Other medications, as well supportive therapies such as physiotherapy, and sometimes surgery, can also be useful.

The discovery of alpha-synuclein bonding to mitochondria provides hope of effective new treatments for PD being invented in the future. While a cure might not yet be around the corner, the researchers at least now know where they need to aim at.

 

Sources: https://en.wikipedia.org/wiki/Parkinson%27s_disease, https://en.wikipedia.org/wiki/Pars_compacta, https://en.wikipedia.org/wiki/Alpha-synuclein#Clinical_significance, http://www.nhs.uk/Conditions/Parkinsons-disease/Pages/Treatment.aspx, https://www.atrainceu.com/course-module/2441043-143_parkinsons-module-02, http://www.parkinson.org/understanding-parkinsons/what-is-parkinsons/The-Stages-of-Parkinsons-Disease, http://stm.sciencemag.org/content/8/342/342ra78

 

 

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