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Biology subjects

Kim, M. I.

Publications and source records attributed to Kim, M. I..

2 recordsLinked to original sources

Alzheimer's disease associations with increased Biondi body amyloid in hippocampal-associated choroid plexus epithelial cells and ependymal cells

To resolve discrepancies in the literature regarding the association between Alzheimers disease (AD) and Biondi body (BB) amyloid in choroid plexus epithelial cells (CPECs), we investigated postmortem hippocampal paraffin blocks with and without a neuropathological diagnosis of AD (n=26-27 each). Similar to previous studies, age was associated with an increased fraction of hippocampal-associated CPECs bearing thioflavin S-positive BBs (p=0.004). In addition, we found that paraffin block storage time was associated with decreased BB detectability (p=0.038) while sex had no effect (p=0.577). Controlling for age, sex, and storage time, AD was associated with a near-significant increase in the BB-containing CPEC fraction (p=0.066) and a significantly greater load of BB-like amyloid in hippocampal-associated ependymal cells (p=0.032). The AD-BB association contrasts with our findings on choroid plexus from the atrium of the lateral ventricle, which lacked this association. We discuss potential explanations for the apparent discrepancy such as regional amyloid cross-seeding.

pathology↗

Massively parallel screening of TIR-derived peptides reveals vast TLR-targeting immunomodulatory peptides

Toll-like receptors (TLRs) are critical regulators of the immune system, and altered TLR responses lead to a variety of inflammatory diseases. Interference of intracellular TLR signaling, which is mediated by multiple Toll/interleukin-1 receptor (TIR) domains on all TLRs and TLR adapters, is an effective therapeutic strategy against immune dysregulation. Peptides that inhibit TIR-TIR interactions by fragmenting interface residues have potential as therapeutic decoys. However, a systematic method for discovering TIR-targeting moieties has been elusive, limiting exploration of the vast unsequenced space of the TIR domain family. Here, we developed a comprehensive parallel screening method to uncover novel TIR-binding peptides derived from previously unexplored surfaces on a wide range of TIR domains. We constructed a large peptide library, named TIR surfacesome, by tiling surface sequences of the large TIR domain family and screening against MALTIR and MyD88TIR, TIRs of two major TLR adaptor proteins, resulting in the discovery of hundreds of TIR-binding peptides. The selected peptides inhibited TLR signaling, demonstrated anti-inflammatory effects in macrophages and therapeutic potential in mouse inflammatory models. This approach may facilitate the development of TLR-targeted therapeutics.

molecular biology↗