Hyperphosphorylated isoforms of the microtubule-associated protein tau are the major components of @entity75 in @entity195 ( @entity195 ). @entity20433 is a major phosphatase implicated in tau dephosphorylation in vitro. Dephosphorylation of tau can be blocked in vivo by @entity18398 , a potent inhibitor of @entity20433 . Moreover, activity of @entity20433 is reduced in @entity195 brains. To elucidate the role of @entity20433 in tau phosphorylation and pathogenesis, we expressed a dominant negative mutant form of the catalytic subunit Calpha of @entity20433 , @entity70278 , in @entity19 by using a neuron-specific promoter. We obtained @entity19 with high expression levels of Calpha @entity70278 in cortical, hippocampal, and cerebellar neurons. @entity20433 activity in brain homogenates of @entity19 was reduced to 66%. Endogenous tau protein was hyperphosphorylated at distinct sites including the AT8 epitope Ser-202/Thr-205, a major @entity195 . AT8-positive tau aggregates accumulated in the soma and dendrites of cortical pyramidal cells and cerebellar Purkinje cells and co-localized with ubiquitin. Our data establish that @entity20433 plays a crucial role in tau phosphorylation. Our results also show that reduced @entity20433 activity is associated with altered compartmentalization and ubiquitination of tau, resembling a key pathological finding in @entity195 .

Reduced protein phosphatase 2A activity induces hyperphosphorylation and altered compartmentalization of tau in XXXX .

@entity75 :: ('MESH:D001927', 'Disease') :: ['neurofibrillary lesions'] @entity20433 :: ('51792(Tax:10090)', 'Gene') :: ['PP2A', 'Protein phosphatase (PP) 2A'] @entity19 :: ('10090', 'Species') :: ['mice', 'transgenic mice'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', "Alzheimer's disease", 'AD-associated tau phosphoepitope'] @entity18398 :: ('MESH:D019319', 'Chemical') :: ['okadaic acid'] @entity70278 :: ('p|SUB|L|199|P', 'ProteinMutation') :: ['L199P']
@entity19 :: (10090,Species) :: ['transgenic mice']
