Biomedical subjects

A M Gillian

Publications and source records attributed to A M Gillian.

4 recordsLinked to original sources

PubMed1999

The role of the protein glycosylation state in the control of cellular transport of the amyloid beta precursor protein.

The amyloid beta precursor protein can exist as both a membrane-bound and a secreted protein, with the former having the potential to generate the amyloid beta peptide present in the neuritic plaques which are characteristic of Alzheimer's disease. In this study, we have used a clone of the AtT20 mouse pituitary cell line which expresses high levels of the amyloid beta precursor protein to characterize the glycosylation state of the secreted and membrane-bound forms of the protein and to examine the role of post-translational modifications in protein processing. Lectin blot analysis of immunoprecipitated amyloid beta precursor protein demonstrated that the soluble form of the protein contains significant amounts of sialic acid, with the lectin staining being reduced in the particulate cellular fractions. Treatment of the cells with mannosidase inhibitors to interfere with the formation of complex-type N-linked glycans resulted in a decrease in secreted amyloid beta precursor protein and an increase in the level of the cellular form of the protein. The increase in amyloid beta precursor protein levels in the cellular fraction was accompanied by an increase in perinuclear staining. Furthermore, cells overexpressing the alpha2,6(N)-sialyltransferase enzyme also demonstrated an increase in amyloid beta precursor protein secretion. These results suggest that the presence of terminal sialic acid residues on complex-type N-glycans may be required for the optimal transport of the amyloid beta precursor protein from the Golgi to the cell membrane with the subsequent cleavage to generate the secreted form of the protein.

1-Deoxynojirimycin↗

PubMed1997

Individual isoforms of the amyloid beta precursor protein demonstrate differential adhesive potentials to constituents of the extracellular matrix.

The amyloid beta precursor protein (AbetaPP) can exist as a membrane-bound glycoprotein which modulates neural cell adhesion. The adhesion of clones of the AtT20 mouse pituitary cell line, transfected with cDNA coding for the 695 (AbetaPP695) and 751 (AbetaPP751) amino acid forms of the protein, to individual components of the extracellular matrix was determined using a centrifugal shear assay. On laminin, poly-L-lysine, fibronectin, and uncoated glass substrata, the cells transfected with AbetaPP695 (6A1 cells) demonstrated a 50% increase in adhesivity over nontransfected cells, while those transfected with AbetaPP751 (7A1 cells) showed a significant decrease in adhesion. There was, however, a significant increase in the adhesive strength of the 7A1 cells to collagen type IV with no change in the adhesivity of the 6A1 cells when compared with control. These changes in adhesivity could be attributed to changes in the levels of the membrane-bound protein and were not due to the interaction of soluble AbetaPP with elements of the extracellular matrix. These studies provide evidence for differential adhesivities of the constituent AbetaPP isoforms and the possible role of the Kunitz protease inhibitor (KPI) domain in influencing the adhesive properties of the protein backbone.

Amyloid beta-Protein Precursor↗

PubMed1994

Expression of the neural cell adhesion molecule (NCAM) in Alzheimer's disease.

Expression of the nerve cell adhesion molecule, NCAM, was examined in post-mortem brain samples from patients with Alzheimer's disease (AD) and from age-matched controls. Four major isoforms of NCAM were identified by Western blot analysis 195, 185, 145 and 120 kDa with no differences being observed in either the intensity of individual band staining or in the expression of the constituent NCAM isoforms in AD when compared with controls. Immunohistochemical staining revealed star-shaped NCAM-positive structures with numerous radiating 'processes' or a more protoplasmic shape with short and thick 'processes'. These structures were not obviously more abundant in AD and there was no NCAM immunoreactivity in neuritic plaques or neurofibrillary tangles. This evidence suggests there is no change in NCAM expression in AD.

Aged↗

PubMedDate not supplied

A decrease in serum sialyltransferase levels in Alzheimer's disease.

A reliable antemortem serum marker for Alzheimer's disease (AD) would be of great importance for the early detection and subsequent therapeutic management of the disease. We have noted a significant decrease in serum levels of the soluble form of the sialyltransferase enzyme in a group of AD patients when compared with both age-matched elderly (over 60 years) and young (under 60 years) controls. In a population of Down's syndrome patients, who develop AD pathology with increasing age, there was an age-related decrease in serum sialyltransferase activity in patients from 20 to 60 years to approach enzyme levels similar to those observed in the AD group. This significant decrease in serum sialyltransferase levels observed may both prove a useful peripheral early biochemical marker of neurodegeneration and provide an indication of the underlying cellular events that occur during the process of nerve cell death in AD.

Adult↗