Before the ALS awareness social media frenzy, the term “ice bucket challenge” meant nothing more to me than the 5+ month reality of living in Minnesota, also known as winter. The ceremonious dumping of ice became a phenomenon of Facebook friends and celebrities alike, but many jumped on the ice bucket bandwagon without much thought to the disease behind it other than a donation. While the challenge spread awareness about ALS, many don’t actually know what happens in the disease. Let’s break the ice and break down ALS, shall we?
ALS stands for amyotrophic lateral sclerosis, an adult-onset neurodegenerative disease characterized by major motor neuron loss in the brain stem, spinal cord, and cerebral cortex. Motor neurons are nerve cells in the brain and spinal cord that send signals out to muscles, telling them when and how to move. As motor neurons degenerate and die in ALS, signals get sent at random, uncoordinated rates, and eventually no message is transmitted at all. When the signals are sent spastically, this causes muscle spasms, also referred to as fasciculations. When the motor neurons die, the muscles no longer receive signals telling them to move and they atrophy, or waste away. Defining characteristics of ALS are muscle weakness, spasms, and atrophy. The muscle atrophy gets progressively worse, and those affected have difficulties swallowing, chewing and speaking and eventually become paralyzed. The body withers away, but someone affected with ALS is painfully aware of losing motor functions and control, and within a few years, losing their life.
How are these messages sent and how does it go so wrong in ALS? Glutamate, a major excitatory neurotransmitter in the brain, is released and helps transmit a message from one motor neuron to another, eventually leading to muscle movement. It binds to two receptors, AMPA and NMDA. Glutamate is an important neurotransmitter that is also involved in many other important functions like learning and memory. When too much glutamate is present, it overexcites neurons and they die, a concept known as excitotoxicity. The article discussed in my Neurochemistry class at Concordia College focused on the role of NMDA receptors.
For many of you, the term “NMDA receptor” may provoke a similar reaction to that of the knights in Monty Python when confronted with the flesh-eating rabbit. Don’t fret; let’s use this castle theme to help explain the role of the NMDA receptor.
Think of a motor neuron as a castle and the NMDA receptor as the gate entrance. Glutamate is like a gatekeeper at the NMDA entrance; it is bound to the door and allows a certain amount of people in. The people represent calcium. As more people enter the castle, they create energy that excites the atmosphere inside the castle, and the excitement spreads. However, if there are too many gatekeepers at the entrance (too much glutamate), it becomes chaotic and they let too many people in the castle. The inside of the castle becomes overcrowded (too much calcium in the cell) and the energy turns from excitement to chaos, causing things to break in the castle. Eventually, the castle (motor neuron) is destroyed. In terms of ALS, massive amounts of motor neurons die in the spinal cord, causing motor deficits and eventually paralysis and death.
Unfortunately, the mechanisms behind motor neuron degeneration in ALS are not as simple as a castle analogy. NMDA is not the only receptor involved, and there are many other contributing factors to the progressive motor neuron loss. However, with more knowledge about receptors like NMDA and their role in the motor neuron death, we can more accurately target the mechanisms for treatment. Current treatments for ALS are limited but target the excessive amounts of glutamate (the gatekeepers in the castle example) in hopes of lowering glutamate levels and slowing the motor neuron degeneration. Though the general public cannot directly find the cure, we can support the cause by becoming educated on diseases like ALS in addition to supporting research funding.
Credits: The article discussed can be found here: http://www.sciencedirect.com/science/article/pii/S0925443912002736
Images used via Google search: ALS image from http://www.bestonlinemd.com/what-is-amyotrophic-lateral-sclerosis-or-als/
Monty Python image from: http://i.imgur.com/hJDbC6o.jpg?3
NMDA receptor image from: http://knowingneurons.com/2013/01/30/ltp-when-neurons-make-a-long-term-commitment/
**”Monty Python and the Holy Grail” is a British comedy and is not associated with ALS or its pathology**
Behind the Bucket: A mechanism behind ALS appears to be too much of a good thing
