TI - Cell -cycle and signal transduction . AB - Expression of cell cycle-related proteins fueled the hypothesis that post-mitotic neurons attempting to reactivate cell -cycling contribute to neurodegeneration in AD [31] -[35] . We analyzed selected markers to pinpoint an eventual role in tau-mediated neurodegeneration ( Table S2 ) . Among cell -cycle and related markers , cyclinD2 and cyclinB1 were strongly up-regulated 3 weeks p.i.in degenerating neurons in AAV-Tau mice ( Figure 8A ) corroborated by other markers , e.g . PCNA and PHOSphorylated retinoblastoma protein (Figure 8A) . Conversely , cell -cycle inhibitor p27KIP1 was strongly down-regulated , while markers like Ki67 and cdk2 were hardly affected by tau-mediated neurodegeneration ( Figure 8A ; results not shown ) . Effects on these and other markers were restricted to sub regions and/or sub-sets of neurons in AAV-Tau mice , while most were unaffected in AAV-EGFP or AAV-APP.SLA injected mice ( results not shown ) . Ras -dependent mitogen-activated protein ( MAP ) kinases control cell -proliferation and stress responses . Expression of activated , phosphorylaTED forms of three members of the MAPK family by IHC revealed no signal for phosphorylaTED SAPK/JNK , whereas PHOSphorylated p44/42 MAPK was elevated mainly in glia cells . Only PHOSphorylated p38 MAPK was observed in a subset of degenerating neurons ( Figure 8B ) . The strong expression of cyclinD2 , i.e.the only D-type cyclin expressed in dividing cells derived from neuronal precursors in adult hippocampus [35] prompted us to inject cyclinD2 deficient mice intracerebrally with AAV-Tau.lt @@@@@ gt P301L . Neurodegeneration in cyclin D2 deficient mice was , however , similar to that in wild-type littermates at 3 weeks p.i.of AAV-Tau.lt @@@@@ gt P301L (Figure 8C) , excluding cyclinD2 on its own as decisive factor in the observed neurodegeneration .