Mi Hee Lim

Neurodegenerative diseases pose a substantial socioeconomic burden on society. Unfortunately, the aging world population and lack of effective cures foreshadow a negative outlook. Although a large amount of research has been dedicated to elucidating the pathologies of neurodegenerative diseases, their principal causes remain elusive. Metal ion dyshomeostasis, proteopathy, oxidative stress, and neurotransmitter deficiencies are pathological features shared across multiple neurodegenerative disord

Alzheimer's disease (AD) is characterized by an imbalance between production and clearance of amyloid-β (Aβ) species. Aβ peptides can transform structurally from monomers into β-stranded fibrils via multiple oligomeric states. Among the various Aβ species, structured oligomers are proposed to be more toxic than fibrils; however, the identification of Aβ oligomers has been challenging due to their heterogeneous and metastable nature. Multiple techniques have recently helped us gain a better under

This tutorial review presents descriptions of two amyloidogenic proteins, amyloid-β (Aβ) peptides and islet amyloid polypeptide (IAPP), whose misfolding propensities are implicated in Alzheimer's disease (AD) and type II diabetes, respectively. Protein misfolding diseases share similarities, as well as some unique protein-specific traits, that could contribute to the initiation and/or development of their associated conditions. Aβ and IAPP are representative amyloidoses and are used to highlight

The reaction of [Fe(II)(tris(2-pyridylmethyl)amine, TPA)(NCCH(3))(2)](2+) with 1 equiv. peracetic acid in CH(3)CN at -40 degrees C results in the nearly quantitative formation of a pale green intermediate with lambda(max) at 724 nm ( epsilon approximately 300 M(-1).cm(-1)) formulated as [Fe(IV)(O)(TPA)](2+) by a combination of spectroscopic techniques. Its electrospray mass spectrum shows a prominent feature at mz 461, corresponding to the [Fe(IV)(O)(TPA)(ClO(4))](+) ion. The Mössbauer spectra r

A series of FL(n) (n = 1-5) ligands, where FL(n) is a fluorescein modified with a functionalized 8-aminoquinoline group as a copper-binding moiety, were synthesized, and the chemical and photophysical properties of the free ligands and their copper complexes were investigated. UV-visible spectroscopy revealed a 1:1 binding stoichiometry for the Cu(II) complexes of FL(1), FL(3), and FL(5) in pH 7.0 buffered aqueous solutions. The reactions of FL(2) or FL(4) with CuCl(2), however, appear to produc

Nitric oxide, a reactive free radical, regulates a variety of biological processes. The absence of tools to detect NO directly, rapidly, specifically, and selectively motivated us to synthesize metal-based fluorescent probes to visualize the presence of NO. We prepared and investigated Co(II), Fe(II), Ru(II), Rh(II), and Cu(II) complexes as turn-on fluorescent NO sensors. Our exploration has provided insight into how the interaction of transition-metal centers with nitric oxide can be utilized f

Two copper(II) complexes containing dansylated ligands were investigated as turn-on fluorescence-based nitric oxide (NO) sensors. Upon addition of NO (g), the quenched fluorescence of both complexes was restored in both organic and buffered aqueous solutions, which is caused by the formation of a diamagnetic Cu(I) species and protonation of the sulfonamide functionality of the ligands. The NO detection limit of these Cu(II) complexes is 10 nM.

The luminescent characteristics of Ru(bpy)(2)dppz(2+) (dppz = dipyrido[3,2-a:2',3'-c]phenazine), a DNA light switch, were investigated in the presence of oligonucleotides containing single base mismatches or an abasic site. In water, the ruthenium luminescence is quenched, but, bound to well matched duplex DNA, the Ru complex luminesces. Here we show that with DNAs containing a defect, rac-, Delta-, and Lambda-Ru(bpy)(2)dppz(2+) exhibit significant luminescent enhancements above that with well m

Cholesterol and metal ions have been suggested to be associated with the onset and progression of Alzheimer's disease (AD). Moreover, recent findings have demonstrated a potential interconnection between these two factors. For example, (a) cholesterol has been shown to be misregulated in AD-afflicted brains, and the aberrant activity of proteins (particularly, apolipoprotein E (ApoE) and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR)) has been linked to cholesterol-related AD e

Berry good news for the brain: Reactivity of myricetin, a naturally occurring flavonoid (see chemical structure), was investigated in relation to metal-associated amyloid-β (Aβ) species. Myricetin was preferentially effective against metal-associated Aβ over metal-free Aβ species, and was able to modulate metal-induced Aβ aggregation and neurotoxicity in vitro and in human neuroblastoma cells. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such docu

A catecholamine neurotransmitter, dopamine (DA), is suggested to be linked to the pathology of dementia; however, the involvement of DA and its structural analogues in the pathogenesis of Alzheimer's disease (AD), the most common form of dementia, composed of multiple pathogenic factors has not been clear. Herein, we report that DA and its rationally designed structural derivatives (1-6) based on DA's oxidative transformation are able to modulate multiple pathological elements found in AD [i.e.,

The ruthenium(II) porphyrin fluorophore complexes [Ru(TPP)(CO)(Ds-R)] (TPP = tetraphenylporphinato dianion; Ds = dansyl; R = imidazole (im), 1, or thiomorpholine (tm), 2) were synthesized and investigated for their ability to detect nitric oxide (NO) based on fluorescence. The X-ray crystal structures of 1 and 2 were determined. The Ds-im or Ds-tm ligand coordinates to an axial site of the ruthenium(II) center through a nitrogen or sulfur atom, respectively. Both exhibit quenched fluorescence wh