Journal News

Neurodegenerative disease linked to microtubules

Laura Elyse McCormick
Jan. 26, 2023

First characterized in Quebec in 1978, autosomal recessive spastic ataxia of Charlevoix–Saguenay, or ARSACS, is a hereditary neurodegenerative disease. Symptoms such as difficulty walking often appear in early childhood and continue to progress, limiting the mobility and lifespan of those affected.

In particular, ARSACS affects the cerebellum, the region of the brain that controls motor skills. It is the second most common recessive form of ataxia, or loss of muscle coordination and movement, in the world.

Purkinje neurons, shown in red here, are nerve cells in the cerebellum.
YINGUA MA & TIMOTHY VARTANIAN, CORNELL UNIVERSITY/NIH IMAGE GALLERY
Purkinje neurons, shown in red here, are nerve cells in the cerebellum.

No cure exists for ARSACS, but in 2000, a team at McGill University identified mutations in the protein sacsin as its cause. Developing therapeutics is a challenge, however, because researchers do not completely understand sacsin’s function. Although previously published work suggests sacsin may influence mitochondrial transport and function in neurons, its role in the cell is still unclear.

Vincent Francis, a postdoctoral fellow at McGill University, joined the laboratory of Peter McPherson because he was interested in neurodegeneration. In particular, Francis wanted to work on the understudied sacsin.

“I decided to pursue the project to understand the cellular function of sacsin, which could provide potential new therapeutic strategies for the treatment of the disease,” Francis wrote to ASBMB Today.

Previous work in the lab had focused on mitochondria, so Francis began looking at the transport of other organelles. He focused on the lysosome, the recycling center of the cell, where unwanted materials can be broken down and reused. Generally, lysosomes are clustered neatly around the nucleus. However, in cells without sacsin, lysosomes were scattered all around.

Lysosomes and other organelles are transported on microtubules. In neurons without sacsin, lysosomes move less. Based on their observations, Francis and the team hypothesized that sacsin could regulate the trafficking of cargo on microtubules.  

“We assumed that sacsin could probably be functioning as an adaptor for organellar transport,” Francis wrote. “Instead, what surprised us was the ability of sacsin to bind to microtubules and to modulate microtubule dynamics.”

Microtubules are required for autolysomal reformation, a process in which new lysosomes are formed. Once again, without sacsin, cells showed a decrease in this process.

Because neurons are large, expansive cells, regulation of organelle trafficking is particularly important for their function.

This research, recently published in the Journal of Biological Chemistry, suggests sacsin is a key regulator of cellular traffic. In the future, the team hopes these results will inform research that can help identify treatments for patients with ARSACS.

Francis noted that several other neurological disorders — including Alzheimer’s disease — are associated with decreases in neuronal microtubule stability. This indicates that microtubules may be a promising therapeutic target for ARSACS and other neurodegenerative diseases.

Enjoy reading ASBMB Today?

Become a member to receive the print edition four times a year and the digital edition weekly.

Learn more
Laura Elyse McCormick

Laura McCormick is a graduate student in the Department of Cell Biology and Physiology at the University of North Carolina at Chapel Hill.

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Candy binges can overload your gut microbiome
News

Candy binges can overload your gut microbiome

Nov. 2, 2024

While most Halloween candies contain lots of sugar, some are better for your gut microbiome than others.

Water rescues the enzyme
Essay

Water rescues the enzyme

Oct. 31, 2024

“Sometimes you must bend the rules to get what you want.” In the case of using water in the purification of calpain-2, it was worth the risk.

Virtual issue celebrates water in ASBMB journals
Journal News

Virtual issue celebrates water in ASBMB journals

Oct. 30, 2024

Read a dozen gold open-access articles covering exciting research about the society’s 2024 Molecule of the year.

There are worse things in the water than E. coli
News

There are worse things in the water than E. coli

Oct. 29, 2024

E. coli levels determined whether Olympic swimmers could dive into the Seine this past summer. But are these bacteria the best proxy for water contamination?

Biobots arise from the cells of dead organisms
News

Biobots arise from the cells of dead organisms

Oct. 27, 2024

Given the right conditions, certain types of cells are able to self-assemble into new lifeforms after the organism they were once part of has died.

The shape of molecules to come
News

The shape of molecules to come

Oct. 26, 2024

Researchers explore unique properties of a nanostructure called “switchback DNA” that could have implications in nature and in biomedicine.