Deposition of Amyloid b(Ab) in the brain contributes to neuronal degeneration in Alzheimer�Ls disease (AD). A?À induces neuritic dystrophy, a characteristic feature of AD pathology. In this chapter we focus on the involvement of LIM kinase 1 (LIMK1), actindepolymerizing factor and cofilin (ADF/Cofilin) in Ab-induced dystrophy in AD. ADF/Cofilin is actin-binding proteins that play a central role in actin filament dynamics, and LIMK1 is the kinase that inhibits ADF/Cofilin. Our data indicate that treatment of hippocampal neurons with A?À increases the level of active LIMK1 and inactive ADF/Cofilin. Treatments that prevent ADF/Cofilin inactivation by LIMK1 abolish Ab-induced degeneration. Immunofluorescence analysis of AD brain, and transgenic mice models of AD showed a significant increase in P-LIMK1 in areas affected with AD-pathology. Thus, aberrant activation of LIMK1 by Ab may play a key role in AD pathology.
b(Ab) in the brain contributes to neuronal degeneration in Alzheimer�Ls disease (AD). A?À induces neuritic dystrophy, a characteristic feature of AD pathology. In this chapter we focus on the involvement of LIM kinase 1 (LIMK1), actindepolymerizing factor and cofilin (ADF/Cofilin) in Ab-induced dystrophy in AD. ADF/Cofilin is actin-binding proteins that play a central role in actin filament dynamics, and LIMK1 is the kinase that inhibits ADF/Cofilin. Our data indicate that treatment of hippocampal neurons with A?À increases the level of active LIMK1 and inactive ADF/Cofilin. Treatments that prevent ADF/Cofilin inactivation by LIMK1 abolish Ab-induced degeneration. Immunofluorescence analysis of AD brain, and transgenic mice models of AD showed a significant increase in P-LIMK1 in areas affected with AD-pathology. Thus, aberrant activation of LIMK1 by Ab may play a key role in AD pathology.