Aβ promotes Alzheimer’s disease‐like cytoskeleton abnormalities with consequences to APP processing in neurons

• DOI: 10.1111/j.1471-4159.2010.06643.x
• Publication Date: 2010-03-23T14:48:26Z
• Authors: Ana Gabriela Henr...; Sandra Isabel Vieira; Edgar F. Da Cruz ...; Odete A. B. Da Cr...
• Keywords: Kinesin; Vesicular Transport Proteins; Neurite

J. Neurochem. (2010) 113 , 761–771. Abstract Aβ is proteolytically produced from the Alzheimer’s amyloid precursor protein (APP). Major properties attributed to include neurotoxic effects that contribute disease neurodegeneration. However, can also affect APP processing and trafficking that, in neurons, anterogradelly transported via microtubules a kinesin‐associated manner. Herein we show induce accumulation of intracellular sAPP primary neuronal cultures. Subcellular fractionation studies immunofluorescence analysis revealed upon exposure retention was localized cytoskeleton associated vesicular structures along neurite processes, positive for an N‐terminal antibody negative C‐terminal antibody. These were kinesin light chain 1 (KLC). We confirm alters both actin microtubule networks. It increases F‐actin polymerization report first time decreases α‐tubulin acetylation. The use drugs partially reversed Aβ‐induced on secretion. data here presented causes by inducing alterations network, thus contributing impaired APP/sAPP transport. Moreover, strengthens hypothesis Aβ‐induces neurodegeneration provides potential mechanism action, as axonal transport have been linked pathology.