Research Perspective Volume 15, Issue 4 pp 898—904

Figure 1. Schematic Diagram summarizing the events in neuronal nuclear invagination in AD: Causes and consequences. Oxidative stress and Tau-hyperphosphorylation have been shown to be responsible for nuclear envelope invagination in neurons. Abnormal actin bundling due to tau-hyperphosphorylation and increased oxidative stress result in changes in nuclear lamin and degradation of nuclear lamina proteins by caspase-6 and cathepsin L that are upregulated in AD. The molecular events downstream of nuclear invagination are mediated by changes in chromatin compaction and abnormal gene transcription, including activation of transposons and emergence of ancient retroviruses. Experimental evidence indicate that attenuation of these events may represent new therapeutical approaches.