2 research outputs found
β‑Amyloid and α‑Synuclein Cooperate To Block SNARE-Dependent Vesicle Fusion
Alzheimer’s
disease (AD) and Parkinson’s disease
(PD) are caused by β-amyloid (Aβ) and α-synuclein
(αS), respectively. Ample evidence suggests that these two pathogenic
proteins are closely linked and have a synergistic effect on eliciting
neurodegenerative disorders. However, the pathophysiological consequences
of Aβ and αS coexistence are still elusive. Here, we show
that large-sized αS oligomers, which are normally difficult
to form, are readily generated by Aβ<sub>42</sub>-seeding and
that these oligomers efficiently hamper neuronal SNARE-mediated vesicle
fusion. The direct binding of the Aβ-seeded αS oligomers
to the N-terminal domain of synaptobrevin-2, a vesicular SNARE protein,
is responsible for the inhibition of fusion. In contrast, large-sized
Aβ<sub>42</sub> oligomers (or aggregates) or the products of
αS incubated without Aβ<sub>42</sub> have no effect on
vesicle fusion. These results are confirmed by examining PC12 cell
exocytosis. Our results suggest that Aβ and αS cooperate
to escalate the production of toxic oligomers, whose main toxicity
is the inhibition of vesicle fusion and consequently prompts synaptic
dysfunction
Light-Induced Fluorescence Modulation of Quantum Dot-Crystal Violet Conjugates: Stochastic Off–On–Off Cycles for Multicolor Patterning and Super-Resolution
Photoswitching
or modulation of quantum dots (QDs) can be promising
for many fields that include display, memory, and super-resolution
imaging. However, such modulations have mostly relied on photomodulations
of conjugated molecules in QD vicinity, which typically require high
power of high energy photons at UV. We report a visible light-induced
facile modulation route for QD-dye conjugates. QD crystal violets
conjugates (QD-CVs) were prepared and the crystal violet (CV) molecules
on QD quenched the fluorescence efficiently. The fluorescence of QD-CVs
showed a single cycle of emission burst as they go through three stages
of (i) initially quenched “off” to (ii) photoactivated
“on” as the result of chemical change of CVs induced
by photoelectrons from QD and (iii) back to photodarkened “off”
by radical-associated reactions. Multicolor on-demand photopatterning
was demonstrated using QD-CV solid films. QD-CVs were introduced into
cells, and excitation with visible light yielded photomodulation from
“off” to “on” and “off”
by nearly ten fold. Individual photoluminescence dynamics of QD-CVs
was investigated using fluorescence correlation spectroscopy and single
QD emission analysis, which revealed temporally stochastic photoactivations
and photodarkenings. Exploiting the stochastic fluorescence burst
of QD-CVs, simultaneous multicolor super-resolution localizations
were demonstrated