Project 171356
The human amylin receptor as a target for the actions of amyloid-beta protein in the brain.
The human amylin receptor as a target for the actions of amyloid-beta protein in the brain.
Project Information
| Study Type: | Other Drug_Development |
| Therapeutic Area: | Neurology |
| Research Theme: | Biomedical |
| Disease Area: | Alzheimer's disease |
| Data Type: | Canadian |
Institution & Funding
| Principal Investigator(s): | Jhamandas, Jack H |
| Institution: | University of Alberta |
| CIHR Institute: | Aging |
| Program: | |
| Peer Review Committee: | Systems & Circuits Neurosciences - A |
| Competition Year: | 2008 |
| Term: | 5 yrs 0 mth |
Abstract Summary
In Alzheimer's disease (AD), a loss of brain cells in key brain areas is linked to memory and cognitive deficits observed in this condition. The deposition of amyloid-beta protein in the brain is a primary pathological feature of AD and it is believed that this peptide is highly neurotoxic to brain cells. Animals that are genetically engineered to over-express this protein within the brain show behavioural deficits and changes in brain architecture that mimic the human condition of AD. Work from our laboratory has shown that compounds, which block the amylin receptor in the brain, can protect rat brain cells from toxicity caused by amyloid-beta protein. This raises the possibility of whether a strategy of blocking amylin receptor to protect nerve cells from amyloid-beta protein can also work in human brain cells. It is important to address this question in human brain cells, since unlike people, normally aging mice and rats do not develop an AD-like condition. In this proposal we use human brain cells, that we can grow and maintain in the dish, to determine whether compounds that block the amylin receptor can protect human nerve cells exposed to amyloid-beta protein. We will examine whether amylin receptors are increased in genetically engineered mice that over-express amyloid-beta protein in the brain and in post-mortem brain tissue from Alzheimer's patients. Finally, we will treat the amyloid over-expressing mice with amylin receptor compounds and ascertain whether it is possible to prevent development of behavioural deficits in these animals. At present there is no treatment for AD other than for its symptoms. Studies such as those contained in this proposal may identify newer therapies based on protecting nerve cells from the deleterious effects of amyloid-beta in the brains of AD patients and thus slowing or preventing the disease altogether.
Research Characteristics
This project includes the following research characteristics:
Study Justification
"In this proposal we use human brain cells, that we can grow and maintain in the dish, to determine whether compounds that block the amylin receptor can protect human nerve cells exposed to amyloid-beta protein."
Novelty Statement
"Studies such as those contained in this proposal may identify newer therapies based on protecting nerve cells from the deleterious effects of amyloid-beta in the brains of AD patients and thus slowing or preventing the disease altogether."
Methodology Innovation
investigating the human amylin receptor as a therapeutic target for Alzheimer's disease by testing amylin receptor blockers in human neurons and a transgenic mouse model