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Author(s): Carmen Venegas [1]; Sathish Kumar [2]; Bernardo S. Franklin [3]; Tobias Dierkes [1, 3]; Rebecca Brinkschulte [3]; Dario Tejera [1]; Ana Vieira-Saecker [1]; Stephanie Schwartz [1]; Francesco Santarelli [1]; [...], The spreading of pathology within and between brain areas is a hallmark of neurodegenerative disorders. In patients with Alzheimers disease, deposition of amyloid- is accompanied by activation of the innate immune system and involves inflammasome-dependent formation of ASC specks in microglia. ASC specks released by microglia bind rapidly to amyloid- and increase the formation of amyloid- oligomers and aggregates, acting as an inflammation-driven cross-seed for amyloid- pathology. Here we show that intrahippocampal injection of ASC specks resulted in spreading of amyloid- pathology in transgenic double-mutant APP[sub.Swe]PSEN1[sub.dE9] mice. By contrast, homogenates from brains of APP[sub.Swe]PSEN1[sub.dE9] mice failed to induce seeding and spreading of amyloid- pathology in ASC-deficient APP[sub.Swe]PSEN1[sub.dE9] mice. Moreover, co-application of an anti-ASC antibody blocked the increase in amyloid- pathology in APP[sub.Swe]PSEN1[sub.dE9] mice. These findings support the concept that inflammasome activation is connected to seeding and spreading of amyloid- pathology in patients with Alzheimers disease.

The best-understood gating transition in ion channels is the nuclear-type inactivation of voltage-gated potassium (K(sub v)) channels, which occurs by a 'ball-and-chain' type mechanism. The three-dimensional structure of the ball peptides from two inactivating mammalian (K(sub v)) channels, namely, (Raw(sub 3) (K(sub v)3.4)) and RCK(sub 4) (K(sub v)1.4), was analyzed using nuclear magnetic resonance spectroscopy. Both the inactivation peptides (IPs) of Raw(sub 3) and RCK(sub 4) have compact structures that reveal two phosphorylation sites, the charged and uncharged regions. However, the RCK(sub 4)-IP is more flexible and less ordered in its amino-terminal part.