University of California, San Francisco (UCSF)

Elucidating of the Mechanism of Lamin B1 Dependent Adult Onset Demyelination

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The research I am carrying out is directed towards elucidating the mechanisms of an age related disease called Autosomal Dominant Leukodystrophy (ADLD). ADLD is a progressive fatal disease occurring in the 4th or 5th decade of life. It is characterized by progressive demyelination of the central nervous system. I have shown that ADLD is caused by the duplication of the gene, Lamin B1. Lamin B1 is a major constituent of the nuclear lamina, which is a fibrous meshwork that underlies the inner nuclear membrane. Lamins and the nuclear lamina are known to play an important role both in aging and age related diseases.

To understand the ADLD disease process I propose to use mutliple approaches using mouse and fruit fly models that over express Lamin B1. The mouse model will allow us to identify age related changes in brain tissue and different cell types in the brain that are affected by an increase in Lamin B1. As Lamin B1 plays a role in gene expression, we also plan to carry out microarray studies on different brain regions to determine which genes are affected by Lamin B1 over expression.The fruit fly model will be used to screen for genes that modify the degenerative process caused by increased Lamin B1. This research will not only help identify factors that contribute to myelin maintenance in adults but also provide novel insights into the role of the nuclear envelope proteins in normal aging.