Mass Spectrometric Characterization in Protein Therapeutics Discovery

Mo, Jingjie; Tymiak, Adrienne A.; Chen, Guodong

doi:10.1007/978-1-4419-7862-2_5

Cited by 2 publications

(1 citation statement)

References 261 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, Apta@CDs-mediated photomodulation induced Aβ’s significant mass intensity increase at around 4530 m / z (Figure d). The successive heavier mass shift in the +16–20 Da range from 4514 m / z implies the inclusion of oxygen adducts into Aβ residues such as histidine, methionine, or tyrosine. ,− According to the literature, Aβ oxygenation reduces its hydrophobicity, suppressing the hydrophobic interactions between Aβ residues and their further aggregation. The atomic force microscope (AFM) images shown in Figure e further support that light-powered Apta@CDs under red light have strong inhibitory efficacies against Aβ self-assembly, inducing the formation of only a few small fragments rather than tangled Aβ fibrillar aggregates.…”

Section: Resultsmentioning

confidence: 99%

Photomodulating Carbon Dots for Spatiotemporal Suppression of Alzheimer’s β-Amyloid Aggregation

et al. 2020

View full text Add to dashboard Cite

Extracellular deposition of β-amyloid (Aβ) peptide aggregates is a major characteristic of Alzheimer’s disease (AD) brain. Because Aβ peptide aggregates aggravate neuropathy and cognitive impairment for AD patients, numerous efforts have been devoted to suppressing Aβ self-assembly as a prospective AD treatment option. Here, we report Aβ-targeting, red-light-responsive carbon dots (CDs), and their therapeutic functions as a light-powered nanomodulator to spatiotemporally suppress toxic Aβ aggregation both in vitro and in vivo. Our aptamer-functionalized carbon dots (Apta@CDs) showed strong targeting ability toward Aβ42 species. Moreover, red LED irradiation induced Apta@CDs to irreversibly denature Aβ peptides, impeding the formation of β-sheet-rich Aβ aggregates and attenuating Aβ-associated cytotoxicity. Consequently, Apta@CDs-mediated photomodualtion modality achieved effective suppression of Aβ aggregation in vivo, which significantly reduced the Aβ burden at the targeted sites in the brain of 5xFAD mice by ∼40% and ∼25% according to imaging and ELISA analyses, respectively. Our work demonstrates the therapeutic potential of photomodulating CDs for light-driven suppression against Aβ self-assembly and related neurotoxicity.

show abstract