Project: Research project

Project Details


DESCRIPTION: (Applicant's abstract) Alzheimer's disease (AD) is a
progressive neurodegenerative disease, affecting memory and cognitive
functions. The cholinergic neurons that project into the cerebral cortex
and hippocampus are lost in AD. Since acetylcholine transmission is
involved with learning and memory, restoration of a cholinergic
influence might have therapeutic benefit. Unfortunately, clinical trials
using medications to enhance cholinergic function have reported little
to no improvement in memory. Failure is likely due to the eventual loss
of these neurons.

Since survival of cholinergic neurons requires nerve growth factor (NGF)
and NGF receptors, NGF-mediated neurotrophic effects may be reduced in
AD. TrkA and p75 are receptors on cholinergic neurons that bind to NGF.
Activation of TrkA has been linked with cell survival, while activation
of p75 may be linked to apoptosis. Abeta accumulates in regions
containing cholinergic cell bodies. It is neurotoxic and may interfere
with such NGF mediated responses as the regulation of TrkA levels.
Increase in p75/TrkA ratio could affect the downstream signaling
mechanisms and promote cell death. Alternatively Abeta may interact
directly with p75 and activate death signaling mechanisms. I propose to
study whether the alterations in the p75/TrkA ratio are involved with
he mechanisms that lead to the loss of cholinergic neurons in AD.
StatusNot started


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