Curcumin can reduce inflammation and neurodegeneration, but its chemical instability and metabolism raise concerns, including whether the more stable metabolite tetrahydrocurcumin (TC) may mediate efficacy. We examined the antioxidant, anti-inflammatory, or anti-amyloidogenic effects of dietary curcumin and TC, either administered chronically to aged Tg2576 APPsw mice or acutely to lipopolysaccharide (LPS)-injected wild-type mice. Despite dramatically higher drug plasma levels after TC compared with curcumin gavage, resulting brain levels of parent compounds were similar, correlating with reduction in LPS-stimulated inducible nitric-oxide synthase, nitrotyrosine, F2 isoprostanes, and carbonyls. In both the acute (LPS) and chronic inflammation (Tg2576), TC and curcumin similarly reduced interleukin-1β. Despite these similarities, only curcumin was effective in reducing amyloid plaque burden, insoluble β-amyloid peptide (Aβ), and carbonyls. TC had no impact on plaques or insoluble Aβ, but both reduced Tris-buffered salinesoluble Aβ and phospho-c-Jun NH 2 -terminal kinase (JNK). Curcumin but not TC prevented Aβ aggregation. The TC metabolite was detected in brain and plasma from mice chronically fed the parent compound. These data indicate that the dienone bridge present in curcumin, but not in TC, is necessary to reduce plaque deposition and protein oxidation in an Alzheimer's model. Nevertheless, TC did reduce neuroinflammation and soluble Aβ, effects that may be attributable to limiting JNKmediated transcription. Because of its favorable safety profile and the involvement of misfolded proteins, oxidative damage, and inflammation in multiple chronic degenerative diseases, these data relating curcumin dosing to the blood and tissue levels required for efficacy should help translation efforts from multiple successful preclinical models.Neuroinflammation is implicated in the pathogenesis of many neurodegenerative disorders, including Alzheimer's disease (AD). In AD, several mediators in the inflammation cascade contribute both to neurodegeneration and to the production and accumulation of the β-amyloid peptide, including interleukin (IL)-1β, phospho-c-Jun NH 2 -terminal kinase (pJNK), reactive oxygen species, inducible nitric-oxide synthase (iNOS)-mediated production of reactive nitric oxide species, and lipid peroxidation products (e.g., 8-iso-PGF 2 α) (for review, see Akiyama Address correspondence to: Dr. Sally A. Frautschy, Departments of Medicine/Neurology UCLA, Greater Los Angeles Healthcare System, VA Medical Center, Research 151, 16111 Plummer St., Sepulveda, CA 91343. E-mail: frautsch@ucla.edu. et al., 2000). For AD therapeutics, there is rationale to develop drugs that attenuate inflammatory cascades contributing to neurodegeneration and amyloid production or accumulation. However, there is concern that some anti-inflammatory drugs may interfere with phagocytic clearance of amyloid. Curcumin, a compound known to inhibit inflammation while reducing plaque deposition in AD models, is the yellow pigm...

Background: Various types of Tau aggregates in AD brains may differentially impact neurodegeneration. Results: Curcumin selectively suppresses soluble Tau dimers and corrects molecular chaperone, synaptic, and behavioral deficits. Conclusion: A drug increasing HSPs involved in Tau clearance reduced Tau dimers and improved cognition. Significance: Curcumin that reduced Tau dimers and increased molecular chaperones was efficacious without altering insoluble Tau.

Interface modification is an effective and promising route for developing functional organic field-effect transistors (OFETs). In this context, however, researchers have not created a reliable method of functionalizing the interfaces existing in OFETs, although this has been crucial for the technological development of high-performance CMOS circuits. Here, we demonstrate a novel approach that enables us to reversibly photocontrol the carrier density at the interface by using photochromic spiropyran (SP) self-assembled monolayers (SAMs) sandwiched between active semiconductors and gate insulators. Reversible changes in dipole moment of SPs in SAMs triggered by lights with different wavelengths produce two distinct built-in electric fields on the OFET that can modulate the channel conductance and consequently threshold voltage values, thus leading to a low-cost noninvasive memory device. This concept of interface functionalization offers attractive new prospects for the development of organic electronic devices with tailored electronic and other properties.

The dysregulation of glycogen synthase kinase-3 (GSK3) has been implicated in Alzheimer disease (AD) pathogenesis and in Aβ-induced neurotoxicity, leading us to investigate it as a therapeutic target in an intracerebroventricular Aβ infusion model. Infusion of a specific GSK3 inhibitor SB216763 (SB) reduced a downstream target, phospho-glycogen synthase 39%, and increased glycogen levels 44%, suggesting effective inhibition of enzyme activity. Compared to vehicle, Aβ increased GSK3 activity, and was associated with elevations in levels of ptau, caspase-3, the tau kinase phospho-c-jun N-terminal kinase (pJNK), neuronal DNA fragmentation, and gliosis. Co-infusion of SB corrected all responses to Aβ infusion except the induction of gliosis and behavioral deficits in the Morris water maze. Nevertheless, SB alone was associated with induction of neurodegenerative markers and behavioral deficits. These data support a role for GSK3 hyperactivation in AD pathogenesis, but emphasize the importance of developing inhibitors that do not suppress constitutive activity.

Reversible switching of the mobility of a water microdroplet between rollable and pinned simply by changing the temperature is realized by coordination of the phase transition of a side‐chain liquid‐crystal polymer (SCLCP) with optimized surface roughness of a superhydrophobic surface. The responsive surface has potential applications in microreactor design and microfluidic control systems.

Low-voltage, low-cost, high-performance monolayer field-effect transistors are demonstrated, which comprise a densely packed, long-range ordered monolayer spin-coated from core-cladding liquid-crystalline pentathiophenes and a solution-processed high-k HfO2 -based nanoscale gate dielectric. These monolayer field-effect transistors are light-sensitive and are able to function as reporters to convert analyte binding events into electrical signals with ultrahigh sensitivity (≈10 ppb).

Curcumin, a polyphenolic antioxidant derived from the turmeric root has undergone extensive preclinical development, showing remarkable efficacy in wound repair, cancer and inflammatory disorders. This review addresses the rationale for its use in neurodegenerative disease, particularly Alzheimer's disease. Curcumin is a pleiotropic molecule, which not only directly binds to and limits aggregation of the β-sheet conformations of amyloid characteristic of many neurodegenerative diseases but also restores homeostasis of the inflammatory system, boosts the heat shock system to enhance clearance of toxic aggregates, scavenges free radicals, chelates iron and induces anti-oxidant response elements. Although curcumin corrects dysregulation of multiple pathways, it may exert many effects via a few molecular targets. Pharmaceutical development of natural compounds like curcumin and synthetic derivatives have strong scientific rationale, but will require overcoming various hurdles including; high cost of trials, concern about profitability and misconceptions about drug specificity, stability, and bioavailability.

Organic field-effect transistors (OFETs) featuring a photoactive hybrid bilayer dielectric (PHBD) that comprises a self-assembled monolayer (SAM) of photochromic diarylethenes (DAEs) and an ultrathin solution-processed hafnium oxide layer are described here. We photoengineer the energy levels of DAE SAMs to facilitate the charging and discharging of the interface of the two dielectrics, thus yielding an OFET that functions as a nonvolatile memory device. The transistors use light signals for programming and electrical signals for erasing (≤3 V) to produce a large, reversible threshold-voltage shift with long retention times and good nondestructive signal processing ability. The memory effect can be exercised by more than 10(4) memory cycles. Furthermore, these memory cells have demonstrated the capacity to be arrayed into a photosensor matrix on flexible plastic substrates to detect the spatial distribution of a confined light and then store the analog sensor input as a two-dimensional image with high precision over a long period of time.