Features Partner Sites Information LinkXpress
Sign In
Demo Company

Loss of Sialidase Activity Linked to Alzheimer's Disease in Mouse Model

By BiotechDaily International staff writers
Posted on 16 Dec 2013
Print article
Image: Silver impregnation histopathogic image of amyloid plaques seen in the cerebral cortex of a patient with Alzheimer disease (Photo courtesy of Wikimedia Commons).
Image: Silver impregnation histopathogic image of amyloid plaques seen in the cerebral cortex of a patient with Alzheimer disease (Photo courtesy of Wikimedia Commons).
Loss of sialidase enzyme activity in the brain was linked in a recent study to the formation of toxic amyloid plaques such as those found in the brains of Alzheimer's disease patients.

The protein encoded by the NEU1 (sialidase or neuraminidase) gene is a lysosomal enzyme that cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids. In the lysosome, this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter is also referred to as "protective protein"). Mutations in the NEU1 gene can lead to sialidosis, a lysosomal storage disease of infants and children.

Investigators at St. Jude Children’s Research Hospital (Memphis, TN, USA) worked with a line of mice that they had genetically engineered to lack the NEU1 gene. Results published in the November 14, 2013, online edition of the journal Nature Communications revealed that loss of NEU1 activity was associated with a lysosomal build-up of amyloid precursor protein (APP). Improperly processed APP was fragmented into the toxic peptides that form Alzheimer’s amyloid-beta plaques. Those fragments included amyloid-beta peptide 42 (Abeta-42), which is thought to play a major role in the Alzheimer’s disease process. Indeed, Abeta-42 was detected in the spinal fluid and hippocampus of mice that lacked NEU1, but not in mice with a functional NEU1 gene.

Some of the mice lacking the NEU1 gene and displaying Alzheimer's disease-like symptoms were treated by gene therapy that used a viral vector to reestablish NEU1 activity. The amount of beta-amyloid plaques was substantially reduced in the treated animals.

“The findings suggest that down-regulation of NEU1 and a reduced supply of the enzyme may contribute to the development of Alzheimer’s disease or similar neurodegenerative disorders in some patients,” said senior author Dr. Alessandra d’Azzo, professor of genetics at St. Jude Children’s Research Hospital. “Among the questions we are asking is whether a therapeutic window exists when the enzyme could be used to halt or even reverse the disease.”

Related Links:

St. Jude Children’s Research Hospital

Print article



view channel

Molecular Light Shed on “Dark” Cellular Receptors

Scientists have created a new research tool to help find homes for orphan cell-surface receptors, toward better understanding of cell signaling, developing new therapeutics, and determining causes of drug side-effects. The approach may be broadly useful for discovering interactions of orphan receptors with endogenous, naturally... Read more

Lab Technologies

view channel
Image: The new ambr 15 fermentation micro-bioreactor system was designed to enhance microbial strain screening applications (Photo courtesy of Sartorius Stedim Biotech).

New Bioreactor System Streamlines Strain Screening and Culture

Biotechnology laboratories working with bacterial cultures will benefit from a new automated micro bioreactor system that was designed to enhance microbial strain screening processes. The Sartorius... Read more


view channel

Purchase of Biopharmaceutical Company Will Boost Development of Nitroxyl-Based Cardiovascular Disease Drugs

A major international biopharmaceutical company has announced the acquisition of a private biotech company that specializes in the development of drugs for treatment of cardiovascular disease. Bristol-Myers Squibb Co. (New York, NY, USA) has initiated the process to buy Cardioxyl Pharmaceuticals Inc. (Chapel Hill, NC, USA).... Read more
Copyright © 2000-2015 Globetech Media. All rights reserved.