%0 Journal Article
%T Lithium suppresses A¦Â pathology by inhibiting translation in an adult Drosophila model of Alzheimer¡¯s disease.
%A Oyinkan Sofola-Adesakin
%A Jorge I. Castillo-Quan
%A Charalampos Rallis
%A Luke S. Tain
%A Ivana Bjedov
%A Iain Rogers
%A Li Li
%A Mobina Khericha
%A Melissa Cabecinha
%A J¨¹rg B£¿hler
%A Linda Partridge
%J Frontiers in Aging Neuroscience
%D 2014
%I Frontiers Media
%R 10.3389/fnagi.2014.00190
%X The greatest risk factor for Alzheimer's disease (AD) is age, and changes in the ageing nervous system are likely contributors to AD pathology. Amyloid beta (A¦Â) accumulation, which occurs as a result of the amyloidogenic processing of amyloid precursor protein (APP), is thought to initiate the pathogenesis of AD, eventually leading to neuronal cell death. Previously, we developed an adult-onset Drosophila model of AD. Mutant A¦Â42 accumulation led to increased mortality and neuronal dysfunction in the adult flies. Furthermore, we showed that lithium reduced A¦Â42 protein, but not mRNA, and was able to rescue A¦Â42-induced toxicity. In the current study, we investigated the mechanism/s by which lithium modulates A¦Â42 protein levels and A¦Â42 induced toxicity in the fly model. We found that lithium caused a reduction in protein synthesis in Drosophila and hence the level of A¦Â42. At both the low and high doses tested, lithium rescued the locomotory defects induced by A¦Â42, but it rescued lifespan only at lower doses, suggesting that long-term, high-dose lithium treatment may have induced toxicity. Lithium also down-regulated translation in the fission yeast Schizosaccharomyces pombe associated with increased chronological lifespan. Our data highlight a role for lithium and reduced protein synthesis as potential therapeutic targets for AD pathogenesis.
%K lithium
%K Drosophila
%K Alzheimer's disease
%K translation
%K lifespan
%U http://www.frontiersin.org/Journal/10.3389/fnagi.2014.00190/abstract