Alzheimer’s: The Quest to Save a Neuron (Part I)

24 September 2018 Comments Off on Alzheimer’s: The Quest to Save a Neuron (Part I)

BY AFSHAN NABI (MBG/III)
afshan.nabi@ug.bilkent.edu.tr

Alzheimer’s: The Quest to Save a Neuron (Part I)
Alzheimer’s is a disease in which neurons, the cells in our brains, are destroyed. This happens, as neuroscientist and writer Lisa Genova has put it, through “molecular murder or cellular suicide.” Amyloid beta is a molecule responsible for this “molecular murder.” When amyloid beta is improperly broken down, it becomes sticky, and begins to clump together with other amyloid beta molecules. Eventually these clumps become large enough to block the passage of electrical signals through the neurons. Neurons are not able to survive without the passage of signals through them. Thus, a “power cut” in the neuron caused by blocking due to amyloid beta entails death of the neuron. The following story aims to visualize what it would be like to live in a neuron facing certain death, through the eyes of an unlikely hero: a nano-sized protein called Kinesin that transports things between parts of the cells.


Kin, of the Kinesin family, was a protein living happily in a Neuron. The Neuron was, in Kin’s view, a grand city to live in. The heart of the city was where the Nucleus was. Though Kin had never seen it herself, she had heard tales of the Nucleus being occupied by the fabled DNA. Folks said it was DNA who had created the whole city, by unfolding and allowing some Proteins to read her secrets and translate them into all the creations around Kin. Kin supposed that she too had been born of the DNA in the Nucleus, though she could not remember anything about it. Kin did not much care to think of the miracles happening inside the Nucleus.
She was a simple Kinesin; her job was to walk along the Microtubule highways and carry anything that needed carrying to the Axon Terminal. Kin loved the freedom of walking along the Microtubules. She thought she would rather be there than cooped up in the Nucleus or any of the grander places in the Neuron. She thought she was lucky to be part of the Kinesin family, entrusted with work that was critical for the survival of the Neuron, and yet still allowed as much freedom as she knew what to do with. The best part of her job was talking to the passengers. Kin, in her short life, had found that folks usually talked about themselves eagerly. Kin, in turn, liked to listen. She knew all sorts of strange and marvelous stories from her conversations. She had heard, for instance, that there were other Neurons out there. And they all differed from the Neuron she lived in. It was mind-boggling; someone had told her there were a billion! But the teller of that last tale had been swaying; he had probably been close to being proteolyzed and, judging from the impossible tales he told, had lost all sense. Kin shuddered at the thought of being proteolyzed. All proteins dreaded the day when they would no longer be able to work and as a consequence would be bundled into the barrel of a Proteasome (another protein) and broken down into tiny pieces that would then be used to build somebody else.
With this last thought she turned her attention to the passenger she was carrying. She knew it was a Proteasome from the barrel shape, lidded at both ends. Proteasomes were feared because, as related above, they were the ones who destroyed proteins that could no longer function. Kin knew she would see one herself at the end of her lifetime. But at present, in the prime of her youth and able to work effortlessly, Kin did not hold her destiny against the Proteasomes; like everybody else, they did the work they had been created to do.
“You seem agitated,” she said, as politely as she could. “Is everything well?”
The Proteasome shifted. “All is well,” he said shortly.
Slightly annoyed by his rudeness, she continued nonchalantly, “I heard the other day that a large group of Amyloid Beta were found outside the Axon and that they were responsible for the power shortage we had a few days ago. No wonder everybody is on edge.”
The Proteasome shivered but said nothing.
Even though Kin had meant to shake his composure, she was hard-pressed to hold back a shiver herself. In the Neuron, a prolonged power shortage meant the death of the whole city.
Kin allowed the silence to stretch out. Then she said, “And I also heard from a reliable guy who works in the Membrane that the Neuron next to ours is dead.”
This time, the Proteasome actually jumped off her. She turned to look at him in surprise. Other Kinesins behind them were forced to stop as well, since Kin and the Proteasome were blocking the road. Kin began to hear irritated murmurs; Kinesins were unforgiving of anything that blocked the Microtubule and kept them from reaching their destinations. Just as she opened her mouth to tell him that they were going to be pushed off the Microtubule if he did not get back on, he grabbed her and pulled her along with him off the Microtubule.
He began fiercely, but his tone and expression grew colder with every word. “Do not go around spreading filthy tales, trying to scare people, little Kinesin, unless your mind is gone and…” He trailed off, looking at her meaningfully.
She did not have to hear the rest of the sentence; he was threatening to proteolyze her! The thought struck a spark of fear in her heart, and she involuntarily stepped back from him.
He nodded in satisfaction, then turned his back to her and hailed a Kinesin without a passenger from the Microtubule. She stood there, frozen, as he disappeared into the distance, his barrel swaying with every step the Kinesin took.

At the Axon Terminal

The Proteasome walked over to a subdued group who, when they saw him, stopped surveying the pulsing Membrane and talking with Proteins who had entered the Neuron. He paused; then like an executioner announced, “The tales are spreading and there is little I can do to hold them back. Some citizens know of the Amyloid Beta being the reason for the power cut we had. They also know about the next Neuron being destroyed.”

His declaration was greeted by a dead silence.

To be continued…