Dataset Information

Overexpression of the IGF-II/M6P receptor in mouse fibroblast cell lines differentially alters expression profiles of genes involved in Alzheimer's disease-related pathology.

ABSTRACT: Alzheimer's disease (AD) is the most common type of senile dementia affecting elderly people. The processing of amyloid precursor protein (APP) leading to the generation of ?-amyloid (A?) peptide contributes to neurodegeneration and development of AD pathology. The endocytic trafficking pathway, which comprises of the endosomes and lysosomes, acts as an important site for A? generation, and endocytic dysfunction has been linked to increased A? production and loss of neurons in AD brains. Since insulin-like growth factor-II (IGF-II) receptor plays a critical role in the transport of lysosomal enzymes from the trans-Golgi network to endosomes, it is likely that the receptor may have a role in regulating A? metabolism in AD pathology. However, very little is known on how altered levels of the IGF-II receptor can influence the expression/function of various molecules involved in AD pathology. To address this issue, we evaluated the expression profiles of 87 selected genes related to AD pathology in mouse fibroblast MS cells that are deficient in murine IGF-II receptor and corresponding MS9II cells overexpressing ? 500 times the human IGF-II receptors. Our results reveal that an elevation in IGF-II receptor levels alters the expression profiles of a number of genes including APP as well as enzymes regulating A? production, degradation and clearance mechanisms. Additionally, it influences the expression of various lysosomal enzymes and protein kinases that are involved in A? toxicity. IGF-II receptor overexpression also alters expression of several genes involved in intracellular signalling as well as cholesterol metabolism, which play a critical role in AD pathology. The altered gene profiles observed in this study closely match with the corresponding protein levels, with a few exceptions. These results, taken together, suggest that an elevation in IGF-II receptor levels can influence the expression profiles of transcripts as well as proteins that are involved in AD pathogenesis.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4028253 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Overexpression of the IGF-II/M6P receptor in mouse fibroblast cell lines differentially alters expression profiles of genes involved in Alzheimer's disease-related pathology.

Wang Yanlin Y Thinakaran Gopal G Kar Satyabrata S

PloS one 20140520 5

Alzheimer's disease (AD) is the most common type of senile dementia affecting elderly people. The processing of amyloid precursor protein (APP) leading to the generation of β-amyloid (Aβ) peptide contributes to neurodegeneration and development of AD pathology. The endocytic trafficking pathway, which comprises of the endosomes and lysosomes, acts as an important site for Aβ generation, and endocytic dysfunction has been linked to increased Aβ production and loss of neurons in AD brains. Since i ...[more]

PMID: 24846272

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Dataset Information

Overexpression of the IGF-II/M6P receptor in mouse fibroblast cell lines differentially alters expression profiles of genes involved in Alzheimer's disease-related pathology.

Publications

Overexpression of the IGF-II/M6P receptor in mouse fibroblast cell lines differentially alters expression profiles of genes involved in Alzheimer's disease-related pathology.

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