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

08 October 2018 Comments Off on Alzheimer’s: The Quest to Save a Neuron (Part II)

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

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.” In the previous piece, we met amyloid beta, the molecule responsible for “molecular murder.” Here, we will begin to acquaint ourselves with Tau, the molecule that initiates “cellular suicide.” Tau’s normal function is to stabilize microtubules, the highways inside cells used by other proteins (like our hero Kinesin) to transport things between parts of the neuron. In Alzheimer’s disease, Tau molecules are modified such that they begin to leave the microtubules and instead stick to each other to form “tangles.” This destabilizes and ultimately destroys the microtubules. Destruction of microtubules has profound consequences ̵ for instance, for the transport of nutrients within the cell.
Kin, left reeling after the Proteasome threatened her with proteolysis, was careful to work harder than she ever had before. She completed her trips to the Axon Terminal without dawdling, anxiously looking out for any signs of her being tagged for destruction.
But even preoccupation with the threat of her own impending destruction did not distract her from the rumors that were going around. The next neuron was dead. No, not dead, but murdered by the immune cells, eaten alive and vanished off the face of this brain. The Tau family of her own Neuron was behaving strangely, leaving their places at the Microtubules and forming groups. The amyloid beta group outside had grown. No, the amyloid beta had been cleared away and all was well.
Two more power cuts had left the Neuron reeling; there was panic, barely concealed, among its residents. Kin heard talk of how the power cuts would begin to stretch longer and longer, until the Neuron was left in a perpetual darkness. How the movements of all the folks in the Neuron would slow down until they all froze in their places, leaving a whole city frozen in time, unable to move forward and be part of the future. The Neuron would become a relic, a threat, a thing that was better destroyed. Or eaten alive.
Kin was worried; she had a lingering suspicion that the worst of the rumors were true. She listened carefully, but, wary of the Proteasome’s threat, she never spoke of them to anyone. Instead, she focused on work.
This time, she was carrying a Dynein to the Axon Terminal. The Kinesins and Dyneins were two sides of the same coin; without either, there would be no coin, that is, no transporting things in the neuron. Essentially, each family was like a one-way train. Dyneins were the protein family responsible for carrying things along the Microtubules in the opposite direction as the Kinesins: from the Axon Terminal toward the Nucleus. The Dyneins then had to be carried back to the Axon Terminal by the Kinesins. For their part, the Kinesins could not move toward the Nucleus, and the Dyneins carried them. But though they were all aware of this symbiosis, there was a rivalry between the two families, in which they constantly tried to best each other.
“You Kinesins always do crawl so. It’s a wonder anything reaches the Axon Terminal at all,” the Dynein said.
Usually Kin would have had a cutting reply ready to hurl back at the Dynein, but this time, she was preoccupied with morbid thoughts.
She had heard another disturbing rumor. Just before setting out, another Kinesin had told her that he had seen tangles inside the Neuron. And broken Microtubules. Kin did not want to think about broken Microtubules; she wished she had not heard of them. The Microtubule was the road Kin walked on. Along it, she transported folks who were needed at the Axon Terminal. Along it, Dyneins, like the one she was carrying, transported folks who needed to be at the center of the cell, near the Nucleus. Thinking of broken Microtubules made it necessary to think of folks stranded at either end of the Neuron. It was an unthinkable disaster. Lack of transport was another step toward a certain death. She hoped the Kinesin had been wrong. Or lying. Or repeating a false rumor. But in her heart, she doubted it. No Kinesin would tell such a lie, or repeat such a rumor. For Kinesins, the Microtubules were sacred. Broken Microtubules meant no work for Kinesins, no reason for existing.
She shook her head, trying to shake those unpleasant thoughts right out. All would be well. Too many things in the Neuron could go wrong, but somehow, everything usually righted itself. Every piece fell into place perfectly. The Neuron avoided disasters every day, sometimes by a hair’s breadth, but usually the danger passed before you could think about it. This time, the people in the Neuron were looking into the face of a disaster. But Kin believed it would all work out eventually. It always did. Disasters always seemed to strike the neuron next to them or a Kinesin known to a friend of a friend. Kin realized, with a certain amount of relief and pleasure, that her life was nearly flawless. She liked doing what she was doing. She liked people. She liked talking to them. Disasters were not what she knew. She knew perfect, blessed normalcy.
The Dynein she was carrying tapped her head.
“Stop ignoring me,” he grumbled.
Normally, people tapping her head irritated Kin no end, but the hope rising in her heart after the dark times since meeting with the Proteasome helped her shrug it off, and she turned her face to the Dynein and smiled at him.
“Sorry, I was a little lost. But I’m here now.”
“Yeah, people are scared,” the Dynein said. “Do you really think the Neuron is going to die?”
“No, I think we’ll be all right. We usually are,” Kin said lightly. A happy smile put a glow on her face, as if a light were shining inside her.
The Dynein looked at her smile and felt his own face break into one.
But suddenly he looked beyond her, and his smile vanished. His eyes widened. He shook her and screamed, “Look out!”
Kin whipped her head around and found herself at the edge… of a broken Microtubule. It only took a moment: suddenly the solid Microtubule beneath her feet, which had been a mountain of certainty in her life, crumbled. She had only a moment of shock; most of her being was still filled with the golden hope she had discovered moments before. She fell into the darkness among the other debris of what had once been live proteins, each with a specific function. Now they were all jumbled together haphazardly, all stuck together. And Kin and the Dynein fell into this dark jumble; there was no other moment. In this region of the Neuron, folks were already frozen in time.