Regulation of GTPase and adenylate cyclase activity by amyloid β-peptide and its fragments in rat brain tissue

A Kinetic Analysis of the Mechanism of β-Amyloid Induced G Protein Activation

“…In earlier work, we and others have shown that Ab-induces G protein activation in neuronlike cell membranes and induces GTP hydrolysis by purified G i a and G 0 a subunits Soomets et al, 1999). We showed that specific inhibition of G protein activation in our cells prevented Ab-induced cell toxicity, thus we speculate that Ab-induced G protein activation is an important step in the mechanism of Ab toxicity.…”

“…For example, Ab may cause changes in bulk membrane fluidity (Avdulov et al, 1997;Eckert et al, 2000;Kanfer et al, 1999;Kremer et al, 2000Kremer et al, , 2001Muller et al, 1995Muller et al, , 1998, alterations in ion channel function (Etcheberrigaray et al, 1994;Weiss et al, 1994), increased membrane permeability due to n free radical generation (Butterfield, 1997;Butterfield et al, 1994Butterfield et al, , 1999Varadarajan et al, 2000), direct disruption of membrane integrity (Arispe et al, 1993a(Arispe et al, ,b, 1994a, and membranemediated G protein activation Soomets et al, 1999). The detailed molecular mechanism of the Ab-cell or Abmembrane interaction and the functional consequences of such interactions are still uncertain.…”

Diphenhydramine-induced amnesia is mediated by Gi-protein activation

“…Furthermore, lower Gs␣ levels and unmodified Gi␣ levels were observed in fibroblasts from familial Alzheimer's disease patients (Shanahan et al, 1997). Recently, it has been reported that amyloid ␤-peptides cause toxicity through activation of Gi proteins (Soomets et al, 1999;Rymer and Good, 2001). We can hypothesise that an intact Gi-protein functionality is essential for the induction of amnesia.…”

Differential prevention of morphine amnesia by antisense oligodeoxynucleotides directed against various Gi‐protein α subunits

“…Furthermore, lower Gsa levels and unmodi®ed Gia levels were observed in ®broblasts from familial Alzheimer's disease patients (Shanahan et al, 1997). Recently, it has been reported that amyloid b-peptides cause toxicity through activation of Gi proteins (Soomets et al, 1999;Rymer & Good, 2001). We can hypothesize that an intact Gi-protein functionality is essential for the induction of amnesia.…”