Sook Wern Chua

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Amyloid-β (Aβ) toxicity in Alzheimer's disease (AD) is considered to be mediated by phosphorylated tau protein. In contrast, we found that, at least in early disease, site-specific phosphorylation of tau inhibited Aβ toxicity. This specific tau phosphorylation was mediated by the neuronal p38 mitogen-activated protein kinase p38γ and interfered with(More)
The translocator protein (TSPO) recently emerged as a potential drug target in Alzheimer's disease (AD). This has been fuelled mainly by positron emission topography studies that show the upregulation of TSPO in AD, especially in relation to microgliosis and astrogliosis in amyloid-β and tau pathology. Although data as to the exact role of TSPO in AD is(More)
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and familial ALS accounts for 10% of cases. The identification of familial ALS mutations in the actin-binding protein profilin 1 directly implicates actin dynamics and regulation in the pathogenesis of ALS. The mechanism by which these mutations cause ALS is unknown. In this study(More)
Neuronal excitotoxicity induced by aberrant excitation of glutamatergic receptors contributes to brain damage in stroke. Here we show that tau-deficient (tau-/-) mice are profoundly protected from excitotoxic brain damage and neurological deficits following experimental stroke, using a middle cerebral artery occlusion with reperfusion model.(More)
A series of racemic N-arylalkyl-2-azaadamantan-1-ols (9-15) and the corresponding deoxygenated, achiral N-arylalkyl-2-azaadamantanes (23-29) were synthesized and screened in competition binding assays against a panel of CNS targets. Adamantyl hemiaminals 9-15 displayed generally low affinity for both σ(1) (K(i) values= 294-1950 nM) and σ(2) receptors (K(i)(More)
In our continued exploration of disubstituted piperazine derivatives as sigma (σ) receptor ligands with central nervous system (CNS) activity, a series of N-(2-benzofuranylmethyl)-N'-(methoxyphenylalkyl)piperazines (16-21 and 26-31) were synthesized, anticipating that these ligands would better suit the structural requirements of the current σ(1)(More)
A series of N-substituted 4-azahexacyclo[,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ols incorporating the respective arylalkyl subunits from several known sigma (σ) receptor ligands were synthesized and evaluated for their affinity against σ receptors and dopamine receptors. The hybrid trishomocubane-derived ligands (4-6) showed good selectivity for σ(1)(More)
In Alzheimer's disease, the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed altenusin, a bioactive(More)
We show that changing the number and position of nitrogen atoms in the heteroatomic core of a pyrazolopyrimidine acetamide is sufficient to induce complex binding to wild type human TSPO. Only compounds with this complex binding profile lacked intrinsic effect on glioblastoma proliferation but positively modulated the antiproliferative effects of a(More)
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