Surface-enhanced Raman spectroscopy (SERS)-based protein analysis is a promising alternative to existing early stage diagnoses. However, SERS research conducted thus far accompanies challenges such as nonuniformity of plasmonic nanostructures, irregular coating of analytes, and denaturation of proteins, which seriously limit the practicability of suggested approaches. Here, we introduce a carboxylic acid-functionalized and graphitic nanolayer-coated three-dimensional SERS substrate (CGSS) fabricated by sequential nanotransfer printing. The substrate consists of well-defined, uniform gold nanowire arrays for effective Raman signal enhancement and a strong protein-immobilization layer. With an enhancement factor (EF) of 5.5 × 105, on par with the highest ever reported values, the CGSS allows the detection of protein conformational changes and the determination of protein concentration via Raman measurements. Exploiting the CGSS, we successfully measured the SERS spectra of Alzheimer’s biomarkers, tau protein and amyloid β, based on which secondary structural changes were analyzed quantitatively.

Inhibition of mitochondrial complex I activity is hypothesized to be one of the major mechanisms responsible for dopaminergic neuron death in Parkinson’s disease. However, loss of complex I activity by systemic deletion of the Ndufs4 gene, one of the subunits comprising complex I, does not cause dopaminergic neuron death in culture. Here we generated mice with conditional Ndufs4 knockout in dopaminergic neurons (Ndufs4 cKO) to examine the effect of complex I inhibition on dopaminergic neuron function and survival during aging and upon MPTP treatment in vivo. Ndufs4 cKO mice did not show enhanced dopaminergic neuron loss in the SNpc or dopamine-dependent motor deficits over the 24-month lifespan. These mice were just as susceptible to MPTP as control mice. However, compared to control mice, Ndufs4 cKO mice exhibited an age-dependent reduction of dopamine in the striatum and increased α-synuclein phosphorylation in dopaminergic neurons of the SNpc. We also utilized an inducible Ndufs4 knockout mouse strain (Ndufs4 iKO) in which Ndufs4 is conditionally deleted in all cells in adult to examine the effect of adult onset, complex I inhibition on MPTP sensitivity of dopaminergic neurons. The Ndufs4 iKO mice exhibited similar sensitivity to MPTP as control littermates. These data suggest that mitochondrial complex I inhibition in dopaminergic neurons does contribute to dopamine loss and the development of α-synuclein pathology. However, it is not sufficient to cause cell- autonomous dopaminergic neuron death during the normal lifespan of mice. Furthermore, mitochondrial complex I inhibition does not underlie MPTP toxicity in vivo in either cell autonomous or non-autonomous manner. These results provide strong evidence that inhibition of mitochondrial complex I activity is not sufficient to cause dopaminergic neuron death during aging nor does it contribute to dopamine neuron toxicity in the MPTP model of Parkinson’s disease. These findings suggest the existence of alternative mechanisms of dopaminergic neuron death independent of mitochondrial complex I inhibition.

No abstract

The development of treatment for neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis is facing medical challenges due to the increasingly aging population. However, some pharmaceutical companies have ceased the development of therapeutics for NDs, and no new treatments for NDs have been established during the last decade. The relationship between ND pathogenesis and risk factors has not been completely elucidated. Herein, we review the potential involvement of transient receptor potential (TRP) channels in NDs, where oxidative stress and disrupted Ca 2+ homeostasis consequently lead to neuronal apoptosis. Reactive oxygen species (ROS) -sensitive TRP channels can be key risk factors as polymodal sensors, since progressive late onset with secondary pathological damage after initial toxic insult is one of the typical characteristics of NDs. Recent evidence indicates that the dysregulation of TRP channels is a missing link between disruption of Ca 2+ homeostasis and neuronal loss in NDs. In this review, we discuss the latest findings regarding TRP channels to provide insights into the research and quests for alternative therapeutic candidates for NDs. As the structures of TRP channels have recently been revealed by cryo-electron microscopy, it is necessary to develop new TRP channel antagonists and reevaluate existing drugs.

No abstract

No abstract

Recently, methods that usea carbon-based filler, a conductive nanomaterial, have been investigated to develop composite fillers cont7aining dielectric materials. In this study, we added geometric changes to a carbon fiber, a typical carbon-based filler material, by differentiating the orientation angle and the number of plies of the fiber. We also studied the electrical and electromagnetic shield characteristics. Based on the orientation angle of 0°, the orientation angle of the carbon fiber was changed between 0, 15, 30, 45, and 90°, and 2, 4, and 6 plies were stacked for each orientation angle. The maximum effect was found when the orientation angle was 90°, which was perpendicular to the electromagnetic wave flow, as compared to 0°, in which case the electrical resistance was small. Therefore, it is verified that the orientation angle has more of an effect on the electromagnetic interference shield performance than the number of plies.

No abstract