Rasche, M. | bioRxiv Science

bioRxiv2025

Detection of a Unique Unfolded p53 Conformation (U-p53AZ) in Tissue of Alzheimers Disease Patients

INTRODUCTIONAlzheimers Disease (AD) is a major public health challenge. An AD-specific unfolded form of the p53 protein was identified (U-p53AZ) and data from animal studies suggests it colocalizes with pTau, in neurofibrillary tangles (NFT) METHODSBrain samples of patients with AD, cognitively unimpaired non-AD, and with fronto-temporal dementia (FTD) are being tested, comparing the pattern of U-p53AZ accumulation (using the antibody 2D3A8, developed by Diadem SpA) with accumulation of pTau, beta-amyloid, and TDP-43. RESULTSU-p53AZ accumulates in brain samples from AD, colocalizes with pTau in the NFT, with a small degree of accumulation in neuritic plaques (NP). The intensity of staining correlates with the pTau staining and Braak staging. No staining is observed in samples from cognitively unimpaired non-AD and FTD. DISCUSSIONThis study provides further support to the hypothesis that U-p53AZ is a player in AD pathology, in link with pTau accumulation and Braak staging.

molecular biology↗

bioRxiv2021

A Bioinspired Glycopolymer for Capturing Membrane Proteins in Native-Like Lipid-Bilayer Nanodiscs

Amphiphilic copolymers that directly extract membrane proteins and lipids from cellular membranes to form nanodiscs combine the advantages of harsher membrane mimics with those of a native-like membrane environment. Among the few commercial polymers that are capable of forming nanodiscs, alternating diisobutylene/maleic acid (DIBMA) copolymers have gained considerable popularity as gentle and UV-transparent alternatives to aromatic polymers. However, their moderate hydrophobicities and high electric charge densities render all existing aliphatic copolymers rather inefficient under near-physiological conditions. Here, we introduce Glyco-DIBMA, a bioinspired glycopolymer that possesses increased hydrophobicity and reduced charge density but nevertheless retains excellent solubility in aqueous solutions. Glyco-DIBMA outperforms established aliphatic copolymers in that it solubilizes lipid vesicles of various compositions much more efficiently, thereby furnishing smaller, more narrowly distributed nanodiscs that preserve a bilayer architecture and exhibit rapid lipid exchange. We demonstrate the superior performance of Glyco-DIBMA in preparative and analytical applications by extracting a broad range of integral membrane proteins from cellular membranes and further by purifying a membrane-embedded voltage-gated K+ channel, which was fluorescently labeled and analyzed with the aid of microfluidic diffusional sizing (MDS) directly within native-like lipid-bilayer nano-discs.

biochemistry↗