TY  - JOUR
UR  - http://dx.doi.org/10.3389/fnagi.2014.00190
TI  - Lithium suppresses A? pathology by inhibiting translation in an adult Drosophila model of Alzheimer's disease
KW  - Alzheimer's disease
KW  -  Drosophila
KW  -  lifespan
KW  -  lithium
KW  -  translation
N2  - 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?) 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?42 accumulation led to increased mortality and neuronal dysfunction in the adult flies. Furthermore, we showed that lithium reduced A?42 protein, but not mRNA, and was able to rescue A?42-induced toxicity. In the current study, we investigated the mechanism/s by which lithium modulates A?42 protein levels and A?42 induced toxicity in the fly model. We found that lithium caused a reduction in protein synthesis in Drosophila and hence the level of A?42. At both the low and high doses tested, lithium rescued the locomotory defects induced by A?42, 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.
VL  - 6
A1  - Sofola-Adesakin, O
A1  - Castillo-Quan, JI
A1  - Rallis, C
A1  - Tain, LS
A1  - Bjedov, I
A1  - Rogers, I
A1  - Li, L
A1  - Martinez, P
A1  - Khericha, M
A1  - Cabecinha, M
A1  - Bähler, J
A1  - Partridge, L
Y1  - 2014///
N1  - Copyright © 2014 Sofola-Adesakin, Castillo-Quan, Rallis, Tain, Bjedov, Rogers, Li, Martinez, Khericha, Cabecinha, Bähler and Partridge. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
ID  - discovery1436872
AV  - public
JF  - Front Aging Neurosci
ER  -