ALS is the most common form of motor neuron degenerative disease, affecting adults during mid to late life, occurring in 2-3 per 100,000 people. The disease is characterized by progressive degeneration of upper and lower motor neurons in the brain and spinal cord that leads to muscle weakness and atrophy. In majority of cases ALS is not associated with any known mutations, and the etiology is still poorly understood. It has long been suspected that environmental toxicants play a role in the etiology of ALS. However, how environmental toxicants, such as heavy metals, affect normal development and function of neurons and how they contribute to pathology of ALS and other neurodegenerative disorders are still poorly understood, especially at the molecular level. ? We propose to use a new assay system in Drosophila to study the effects of chronic exposure to environmental toxicants on the structural integrity of neurons in vivo. Unbiased genetic screens will be carried out to identify molecular players whose mutations can either enhance or suppress heavy metal neurotoxicity. These studies represent an innovative approach to examine the effects of environment-gene interactions on neuronal structures, which will likely make significant contributions to our understanding of the molecular mechanisms through which genetic alternations and environmental insults work together to lead to pathological changes involved in neurodegenerative diseases, such as ALS. ? ?
| Li, Wenjun; Li, Yan; Gao, Fen-Biao (2005) Abelson, enabled, and p120 catenin exert distinct effects on dendritic morphogenesis in Drosophila. Dev Dyn 234:512-22 |
