Possible use of sulfated glycosaminoglycans in making a cell culture model of neurofibrillary tangle formation

H. V. Nguyen, Lee-Way Jin

Research output: Contribution to journalArticle

Abstract

Neurofibrillary tangles (NFTs) are one of the major pathological lesions seen in the brains Alzheimer's disease patients. The number and distribution of these lesions have been observed to correlate with the clinical level of dementia in AD patients. Ultrastructurally, NFTs are primarily composed of aggregated tau protein, and have been induced to form in vitro upon incubation of human tau with heparin, a glycosaminoglycan (GAG), at physiological conditions. We attempted to further explore the role of GAGs in NFT formation. A rat neuronal cell line (B103) expressing human tau protein was grown in heparin enriched medium and observed for NFT formation. After a two week observation period under various heparin concentrations, no cellular differences were observed by microscopy or immunohistochemistry between tau expressing and control B103 cells. Possible explanations may be that heparin was either not taken up by the B103 cells, or heparin that was taken up is compartmentalized in endosomes within the cell. Either scenario may explain why our results do not more closely follow in vitro experiments. To improve the experimental protocol, a retroviral vector containing a gene for a perlecan subunit was constructed Perlecan is a proteoglycan containing numerous GAG moieties. It is hoped transfection of B103 cells with this vector will be a more efficient way of introducing GAGs into the cytoplasm of tau expressing B103 cells.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Volume47
Issue number2
StatePublished - Feb 1999
Externally publishedYes

Fingerprint

A73025
Neurofibrillary Tangles
Cell culture
Heparin
Cell Culture Techniques
Glycosaminoglycans
tau Proteins
Endosomes
Brain Diseases
Proteoglycans
Transfection
Dementia
Rats
Microscopy
Brain
Microscopic examination
Alzheimer Disease
Cytoplasm
Genes
Immunohistochemistry

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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title = "Possible use of sulfated glycosaminoglycans in making a cell culture model of neurofibrillary tangle formation",
abstract = "Neurofibrillary tangles (NFTs) are one of the major pathological lesions seen in the brains Alzheimer's disease patients. The number and distribution of these lesions have been observed to correlate with the clinical level of dementia in AD patients. Ultrastructurally, NFTs are primarily composed of aggregated tau protein, and have been induced to form in vitro upon incubation of human tau with heparin, a glycosaminoglycan (GAG), at physiological conditions. We attempted to further explore the role of GAGs in NFT formation. A rat neuronal cell line (B103) expressing human tau protein was grown in heparin enriched medium and observed for NFT formation. After a two week observation period under various heparin concentrations, no cellular differences were observed by microscopy or immunohistochemistry between tau expressing and control B103 cells. Possible explanations may be that heparin was either not taken up by the B103 cells, or heparin that was taken up is compartmentalized in endosomes within the cell. Either scenario may explain why our results do not more closely follow in vitro experiments. To improve the experimental protocol, a retroviral vector containing a gene for a perlecan subunit was constructed Perlecan is a proteoglycan containing numerous GAG moieties. It is hoped transfection of B103 cells with this vector will be a more efficient way of introducing GAGs into the cytoplasm of tau expressing B103 cells.",
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