INIMEC - CONICET 05467
INSTITUTO DE INVESTIGACION MEDICA MERCEDES Y MARTIN FERREYRA
Unidad Ejecutora - UE
capítulos de libros
Título:
Role of LIMK1 in neuronal degeneration in AlzheimerLs Disease
Autor/es:
LORENZO A AND HEREDIA L
Libro:
Neurodegenerative Diseases: From Molecular Concepts to Therapeutic Targets
Editorial:
Nove Science Publishers Inc
Referencias:
Lugar: New York; Año: 2008; p. 39 - 49
Resumen:
Deposition of Amyloid b(Ab) in the brain contributes to neuronal degeneration in AlzheimerLs disease (AD). AÀ 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 AÀ 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 AlzheimerLs disease (AD). AÀ 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 AÀ 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.
