A major goal in clinical and basic neuroscience is to identify factors that can promote the survival of spinal motor neurons. Despite the identification of several neurotrophic factors that can support motor neurons, we are still incapable of rescuing the majority of motor neurons in vivo. The goal of this proposal is to determine the function of a relatively novel receptor tyrosine kinase, Anaplastic Lymphoma Kinase (ALK), in spinal motor neurons. Based on our preliminary data including the fact ALK is dynamically expressed in spinal motor neurons during the period of programmed cell death (PCD), we hypothesize that ALK promotes the survival of spinal motor neurons. We will test this hypothesis by conducting gain and loss-of-function manipulations of ALK expression chick embryos in ovo and determine the effects on spinal motor neuron survival.

Public Health Relevance

If spinal motor neurons die, paralysis results. Motor neurons die in developmental disorders such as Spinal Muscular Atrophy and in adult-onset disorders such as Amyotrophic Lateral Sclerosis (Lou Gehrig's disease) and following spinal cord injury. We have identified a protein, Anaplastic lymphoma kinase, which is expressed on spinal motor neurons. Our preliminary data indicates that reducing levels of this protein causes the death of spinal motor neurons. The goal of this study is to increase levels of this protein to test whether we can rescue dying spinal motor neurons. This work could lead to novel therapeutics for promoting the survival of motor neurons in neural disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Small Research Grants (R03)
Project #
1R03NS065299-01
Application #
7640435
Study Section
Neural Oxidative Metabolism and Death Study Section (NOMD)
Program Officer
Kleitman, Naomi
Project Start
2009-02-15
Project End
2011-01-31
Budget Start
2009-02-15
Budget End
2010-01-31
Support Year
1
Fiscal Year
2009
Total Cost
$71,250
Indirect Cost
Name
Montana State University - Bozeman
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
625447982
City
Bozeman
State
MT
Country
United States
Zip Code
59717