Abstract
Considerable evidence shows critical roles of intracellular pathogenic events of Alzheimer’s disease (AD). In particular, intracellular amyloid-β accumulation and oligomerization are early AD pathologic processes, which may lead to changes in inflammatory molecules and other AD-related pathological components. Curcumin and its analogs have been identified as potential drug candidates for AD. However, the effects of curcumin on intracellular AD pathologic processes remain largely unknown. Here we utilized a recently developed nanoplasmonic fiber tip probe (nFTP) technology and investigated whether curcumin leads to intracellular AD pathologic changes. We showed that our nFTP technology could robustly detect intracellular AD-related protein changes caused by a well-known inflammation inducer and a familial AD mutation. Intriguingly, curcumin remarkably reduced the level of intracellular oligomers while modestly reduced the level of an inflammatory cytokine. Thus, our results provided evidence that curcumin’s mechanism of action in attenuating AD pathology is through a major role of decreasing oligomerization.
Highlights
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder and the primary cause of dementia in the elderly[1]
The sensitivity of the nanoplasmonic fiber tip probe (nFTP) ranges from 0.5 nM to 0.5 μM for tested proteins which have affinity values at 10–100 nM. nFTP technology has several unique advantages compared to fluorescent imaging or immunoassays
We showed that genetic and pharmacological components led to robust AD-related pathologic protein changes, which can be reliably detected by our nFTP technology in single live mammalian cells
Summary
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder and the primary cause of dementia in the elderly[1]. We focus on investigating the effects of curcumin on AD intracellular events through our recently developed nanoplasmonic fiber tip probe (nFTP) technology[38, 39]. This technology provides a quantitative approach to robustly measure intracellular proteins in live, single cells. We asked whether a well-known pharmacological inflammation inducer (lipopolysaccharide; LPS) may influence AD intracellular events that can be attenuated by curcumin We showed that both genetic and pharmacological components led to pronounced changes in intracellular AD-related proteins, including Aβ42, A11-reactive oligomers and an inflammatory cytokine - tumor necrosis factor-α (TNF-α). We provided compelling evidence for the first time that a strong mechanism of action in curcumin toward therapeutics in AD may be through reducing intracellular AD-related proteins, via decreasing oligomerization
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