Leading the worldwide fight to treat and cure
Tay-Sachs, Canavan, GM1 and Sandhoff diseases

2012-2013 Research Initiative Grants

Alessandra d’Azzo, PhD
St. Jude Children's Research Hospital

Studies of the Molecular and Biochemical Bases
of Neurodegeneration in Sialidosis


Scientists from d’Azzo Lab analyzed the effects of NEU1 deficiency in the sialidosis animal model. A set of genes were also identified and studied, as their expression patterns were affected by the loss the enzyme NEU1 and were therefore likely contributors to disease pathogenesis.


Neuraminidase 1 (NEU1) is the key lysosomal enzyme in brain cells that normally are used to digest and either recycle or dispose of glycoproteins. The patients of sialidosis, a rare pediatric lysosomal storage disease, have too little or no enzyme and present with pathologic features that scientists have successfully reproduced in an animal model of the disease.

Researchers at d’Azzo Lab have extensively used the laboratory animals to study mechanisms of pathogenesis linked to NEU1 deficiency. It was previously discovered that NEU1 deficient animals have alterations in the brain that resemble Alzheimer’s disease (AD), a neurodegenerative condition that usually develop in older adults [1]. The finding triggered a hypothesis that NEU1 may represent a risk factor of AD conditions, and could potentially be exploited not only for the treatment of sialidosis but also as a novel therapeutic target for AD.

The current work aimed to further analyze the molecular and biochemical events downstream of NEU1 deficiency. The resulting newly identified genes and their products could potentially be used for diagnostic and therapeutic purposes for both sialidosis and AD patients. The results from this study were published in the journal of Nature Communication 2013 [2].

Link of resulting publication in PubMed.gov: https://www.ncbi.nlm.nih.gov/pubmed/24225533

[1] Zanoteli, E., van de Vlekkert, D., Bonten, E. J., Hu, H., Mann, L., Gomero, E. M., Harris, A. J., Ghersi, G., and d'Azzo, A. Muscle degeneration in neuraminidase 1-deficient mice results from infiltration of the muscle fibers by expanded connective tissue, Biochim Biophys Acta 2010, 1802, 659-672.

[2] Annunziata I., Patterson A., Helton D., Hu H., Moshiach S., Gomero E., Nixon R. & d’Azzo A. Lysosomal NEU1 deficiency affects amyloid precursor protein levels and amyloid-b secretion via deregulated lysosomal exocytosis. Nature Comm. 2013, 4, 3734.