Dec. 3, 2013 — St. Jude Children's Research Hospital scientists have identified an enzyme that can halt or possibly even reverse the build-up of toxic protein fragments known as plaques in the brains of mice with Alzheimer's disease. The research appeared in a recent edition of the scientific journal Nature Communications.
Plaques decreased substantially in mice treated with gene therapy to increase activity of the enzyme neuraminidase 1 (NEU1) in a region of the brain involved in learning and memory. Plaques accumulate between neurons in the brains of Alzheimer's patients and are a hallmark of the disease.
The results raise hopes the enzyme could lead to new methods of diagnosing and treating Alzheimer's disease, a neurodegenerative disorder that causes problems with memory, thinking and behavior. More than 5 million Americans are currently living with the problem. The number is expected to rise as the population ages.
"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 the study's corresponding author Alessandra d'Azzo, Ph.D., a member in the St. Jude Department of Genetics. "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."
NEU1 belongs to a family of enzymes in cells whose job is to dismantle and recycle unneeded proteins and other components. The work is done inside cell structures called lysosomes.
The enzyme is missing or reduced in a rare inherited disorder called sialidosis that can affect children and adolescents. This is the first report linking NEU1 to age-related neurodegenerative disorders like Alzheimer's. In collaboration with the University of California, Davis, D'Azzo and her colleagues have begun checking NEU1 levels in brain tissue of Alzheimer's patients at different stages of the disease.
D'Azzo's long-standing interest in sialidosis and related disorders known as lysosomal storage diseases led to the discovery. The findings include evidence of how the protein fragments that make up the Alzheimer's plaque are deposited outside neurons and how loss of NEU1 possibly contributes to disease progression and spread.
The work was done in a mouse developed in d'Azzo's laboratory that lacked the NEU1 gene. These studies revealed that loss of NEU1 activity was associated with a build-up in lysosomes of the amyloid precursor protein (APP), which they identified as a natural target of the enzyme. Improperly processed, APP is broken into the toxic peptides that form Alzheimer's plaques. Those fragments include amyloid beta peptide 42 (A
Plaques decreased substantially in mice treated with gene therapy to increase activity of the enzyme neuraminidase 1 (NEU1) in a region of the brain involved in learning and memory. Plaques accumulate between neurons in the brains of Alzheimer's patients and are a hallmark of the disease.
The results raise hopes the enzyme could lead to new methods of diagnosing and treating Alzheimer's disease, a neurodegenerative disorder that causes problems with memory, thinking and behavior. More than 5 million Americans are currently living with the problem. The number is expected to rise as the population ages.
"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 the study's corresponding author Alessandra d'Azzo, Ph.D., a member in the St. Jude Department of Genetics. "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."
NEU1 belongs to a family of enzymes in cells whose job is to dismantle and recycle unneeded proteins and other components. The work is done inside cell structures called lysosomes.
The enzyme is missing or reduced in a rare inherited disorder called sialidosis that can affect children and adolescents. This is the first report linking NEU1 to age-related neurodegenerative disorders like Alzheimer's. In collaboration with the University of California, Davis, D'Azzo and her colleagues have begun checking NEU1 levels in brain tissue of Alzheimer's patients at different stages of the disease.
D'Azzo's long-standing interest in sialidosis and related disorders known as lysosomal storage diseases led to the discovery. The findings include evidence of how the protein fragments that make up the Alzheimer's plaque are deposited outside neurons and how loss of NEU1 possibly contributes to disease progression and spread.
The work was done in a mouse developed in d'Azzo's laboratory that lacked the NEU1 gene. These studies revealed that loss of NEU1 activity was associated with a build-up in lysosomes of the amyloid precursor protein (APP), which they identified as a natural target of the enzyme. Improperly processed, APP is broken into the toxic peptides that form Alzheimer's plaques. Those fragments include amyloid beta peptide 42 (A