title: Caffeine modulates tau phosphorylation and affects Akt signaling in postmitotic neurons.
abstract: Neuronal cell cycle reentry, which is associated with aberrant tau phosphorylation, is thought to be a mechanism of neurodegeneration in AD. Caffeine is a neuroprotective drug known to inhibit the cell cycle, suggesting that its neuroprotective nature may rely, at least in part, on preventing tau abnormalities secondary to its inhibitory effect on neuronal cell cycle-related pathways. Accordingly, we have explored in the present study the impact of caffeine on cell cycle-linked parameters and tau phosphorylation patterns in an attempt to identify molecular clues to its neuroprotective effect. We show that caffeine blocks the cell cycle at G1 phase in neuroblastoma cells and leads to a decrease in tau phosphorylation; similarly, exposure of postmitotic neurons to caffeine led to changes in tau phosphorylation concomitantly with downregulation of Akt signaling. Taken together, our results show a unique impact of caffeine on tau phosphorylation and warrant further investigation to address whether caffeine may help prevent neuronal death by preventing tau abnormalities secondary to aberrant entry into the cell cycle.
authors.affiliation: MRC Centre for Neurodegeneration, Department of Neuroscience PO37, Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK. Antonio.Currais@iop.kcl.ac.uk
authors.forename: Antonio
authors.initials: A
authors.lastname: Currais
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kato
authors.forename: Leonides
authors.initials: L
authors.lastname: Canuet
authors.forename: Ryouhei
authors.initials: R
authors.lastname: Ishii
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Tanaka
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
authors.forename: Salvador
authors.initials: S
authors.lastname: Soriano
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D010726:Phosphodiesterase Inhibitors; D016875:tau Proteins; D002110:Caffeine; D051057:Proto-Oncogene Proteins c-akt