Nucleolin could be key to understanding neurodegenerative disorders

By The Science Advisory Board staff writers

November 10, 2022 -- A new study challenges recent theories of the role structures inside the nucleus play in neurodegenerative disorders and suggests the relevance of researching Nucleolin, its function, and how it contributes to these disorders.

Researchers from Mount Desert Island Biological Laboratory in Bar Harbor, ME, found the homolog of the human protein Nucleolin in the transparent roundworm Caenorhabditis elegans (Nature Communications, November 3, 2022). The multifunctional protein is present in many animals, plants, and fungi, but was previously thought to be absent in nematodes. The protein is associated with familial amyotrophic lateral sclerosis (ALS) and Alzheimer's disease, and overall nucleolar dysfunction is linked to neurodegeneration.

Identifying the Nucleolin homolog, named NUCL-1, makes C. elegans a new discovery platform for neuronal functions of Nucleolin and the genetics of related neurodegeneration because the roundworm is suited to in vivo microscopy.

By studying the roundworm, the researchers were able to better understand phase separation and learned that removing a key protein domain of NUCL-1 disrupted nucleolar architecture within reproductive cells, but the mutant worms still developed normally and produced normal offspring. In other words, perhaps nucleus architecture isn't as important as was previously thought. This could be relevant for understanding ALS or Alzheimer's disease where widespread disrupted phase separation is thought to contribute to their development.

The researchers contend the discovery will spark new avenues of study in the fields of phase separation, nucleolar structure and function, as well as Nucleolin-associated human disease, they said.

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