The TAP (tissue plasminogen activator) is the main converter
of plasminogen to plasmin in the brain, where it seems to have a beneficial
role. In fact, it has been used as a drug to reduce brain damage in patients who
have suffered strokes, as in the conversion of plasminogen to plasmin can
dissolve the clots formed. However, you may also have neurotoxic effects, as
reported already in 1998 a team from Harvard Medical School, noting that caused
brain damage in mice the injection of the activator, and can be plasmin
dependent or not.

Little progress was made in seven years on knowledge of
substrates and pathways that mediate the neurotoxicity of TPA plasmin
independent. Now, a collaborative work done at the University of Barcelona,
Hospital del Mar and IMIM Barcelona, the University of Turin and Madrid Neuro
Pharma company, shows that TPA promotes activation of the transduction pathway
regulated kinase Extra cellular Signal (Erk) 1 / 2, which in turn activates the
GSK3 (glycogen synthase kinase 3) in a mechanism involving de novo protein
synthesis, leading to several undesirable processes such as aberrant
phosphorylation of Tau protein (component of helical filaments that accumulate
in Alzheimer’s), destabilization of microtubules, and apoptosis. Effects are
similar to those produced by amyloid aggregates in a TAP-dependent process.

 It therefore seems consistent than in brains of
Alzheimer patients colocalicen high levels of TPA with amyloid-rich areas, ERK1
/ 2 activated and phosphorylated Tau. The work, published in EMBO, is the first
demonstration of involvement of TPA in these aberrant processes, and a
convincing indication of the possible role of this molecule in the pathology of
Alzheimer’s disease.