2.
Much of our current understanding about neurodegenerative diseases can be attributed to the study of inherited forms of these disorders. For example, mutations in the
presenilin 1 and
2 genes have been linked to early onset familial forms of Alzheimer''s disease (FAD). Using the
Drosophila central nervous system as a model we have investigated the role of
presenilin in one of the earliest cellular defects associated with Alzheimer''s disease, intracellular calcium deregulation. We show that expression of either wild type or FAD-mutant
presenilin in
Drosophila CNS neurons has no impact on resting calcium levels but does give rise to deficits in intracellular calcium stores. Furthermore, we show that a loss-of-function mutation in
calmodulin, a key regulator of intracellular calcium, can suppress
presenilin-induced deficits in calcium stores. Our data support a model whereby
presenilin plays a role in regulating intracellular calcium stores and demonstrate that
Drosophila can be used to study the link between
presenilin and calcium deregulation.
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