Veterinary researchers discover a new amyloidosis

Researchers discover a new amyloidosis

Amyloid deposits in canine mammary gland tumor. Credit: Tomoaki Murakami, Tokyo University of Agriculture and Technology

A collaboration led by scientists at the Tokyo University of Agriculture and Technology (TUAT), Japan, has discovered a new amyloid protein from canine mammary tumors. This amyloid protein, α-S1 casein, normally plays a key role in the transport of calcium phosphate as a milk protein that provides infant nutrition, but its involvement in the disease was unknown. In this study, they demonstrated for the first time that α-S1 casein can cause amyloidosis in vivo and elucidated the detailed mechanism of amyloid formation.

The researchers released their findings on Jan. 21 Veterinary pathology.

Amyloidosis is a group of diseases in which amyloid, generated by the misfolding of host proteins, is deposited in different organs. To control the onset and progression of amyloidosis, it is necessary to understand the big picture of the complex pathogenesis of the disease. However, an integrated understanding has not been established and the development of definitive treatments has stalled.

“Amyloidosis associated with canine mammary tumors was first reported in July 1985, but the amyloid precursor protein was unknown. Since I was born in July 1985 and the same age, I had a sense of familiarity with disease,” said Tomoaki Murakami, DVM, Ph.D., the paper’s first and corresponding author and Laboratory Associate Professor of Veterinary Toxicology at TUAT.

They first performed a mass spectrometry-based proteomic analysis on five dogs with mammary tumor-associated amyloidosis and identified α-S1-casein as an amyloid precursor protein. “This finding was surprising because the amyloidogenicity of α-S1 casein was unknown, and its chaperone function was rather thought to regulate the amyloid formation of other milk proteins, such as α-S2 casein and κ-casein”.

Gene analysis revealed that α-S1 casein expression was dozen-fold elevated in individuals with amyloidosis compared with those without amyloidosis. With further analysis using mass spectrometry, they noted that the N-terminal disordered region was lost in α-S1-casein in the amyloid deposits.

“These results clearly support that α-S1 casein acquires its ability to form amyloid through overexpression and truncation of the N-terminal disordered region,” Murakami said. They next cultured recombinant N-terminal truncated α-S1-casein proteins in vitro and found their amyloid formation.

“Because α-S1-casein is also expressed in the mammary glands of humans, we found it necessary to assess the risk in humans,” Murakami said. They then confirmed that synthetic peptides derived from human α-S1-casein form amyloid in vitro and found that α-S1-casein-induced amyloidosis can occur in humans.

“Research into animal disease is essential not only to maintain the health of livestock and pets, but also to gain a deeper understanding of human pathology. In this study, we discovered amyloidosis in dogs, which has not yet been discovery in humans, and also clarified the potential risk of the disease in humans based on in vitro experiments. We expect our results to provide useful information to predict the possible occurrence of amyloidosis in humans,” Murakami added.

More information:
Tomoaki Murakami et al, Identification of a novel amyloidosis in dogs: α-S1-casein acquires amyloidogenicity in mammary tumor by overexpression and N-terminal truncation, Veterinary pathology (2023). DOI: 10.1177/03009858221148511

Provided by Tokyo University of Agriculture and Technology

Quote: Veterinary Researchers Uncover New Amyloidosis (2023, Jan 24) Retrieved Jan 24, 2023 from https://phys.org/news/2023-01-veterinary-uncover-amyloidosis.html

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