The role of Intersectin-1 in endocytic anomalies: implications for Down syndrome and Alzheimer's disease

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/334079

Funding Status
Closed

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Funded Activity Summary

Individuals with Down syndrome have three copies of human chromosome 21, rather than the normal two. We have discovered a gene called Intersectin-1, located on human chromosome 21, that is expressed at higher levels than normal in individuals with Down syndrome. Intersectin-1 has a role in endocytosis, a process whereby cells take up molecules from the outside. Endocytosis occurs in all cells but is highly specialised in the brain where chemical transmitters are released and then rapidly recovered by endocytosis in a process enabling neurones to pass signals to one another. A disturbance in endocytosis has been reported as the earliest hallmark of Alzheimer's disease in both non-Down syndrome and Down syndrome individuals. This disturbance is characterised by the presence of enlarged endosomes (small packages in neuronal cells containing chemical neurotransmitters formed during endocytosis). These enlarged endosomes are present long before the characteristic plaques of Alzheimer's disease appear. Since all individuals with Down syndrome develop Alzheimer's-like neuropathology, there must be a common disease mechanism that can be traced to the extra gene dosage from chromosome 21. We propose that a malfunctioning of Intersectin-1 is this common mechanism and we aim to test our hypothesis by the generation and analysis of mouse models of disrupted endocytosis.

Funded Activity Details

Start Date: 01-01-2005

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $510,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Biochemistry and Cell Biology

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Alzheimer's diseae | Down syndrome | endocytosis | gene knockout | identification of genes leading to disease | neuronal degeneration | synaptic vesicles | vesicle-associated proteins

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