In This Issue Cite This: ACS Chem. Neurosci. 2018, 9, 2520−2520
ACS Chem. Neurosci. 2018.9:2520-2520. Downloaded from pubs.acs.org by 185.50.250.79 on 12/17/18. For personal use only.
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IMAGING A BIOMARKER FOR NEUROINFLAMMATION IN THE BRAIN
Cyclooxygenase-1 (COX-1) is a critical enzyme in several neuronal biosynthetic pathways. COX-1 expression may also play a role in neuroinflammation, and nonsteroidal antiinflammatory drugs, such as aspirin and ibuprofen, inhibit COX-1. Beyond causing headaches, neuroinflammatatory processes are now thought to also play a role in neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease. As a result, the ability to identify biomarkers of inflammation could assist with early diagnostics of these diseases. In this issue, Singh et al. (DOI: 10.1021/acschemneuro.8b00102) design a family of prospective COX-1 radioligands for positron emission tomography imaging. The radioligand candidates were prepared from a 1,5-diaryl-1H-1,2,4-triazole scaffold, and several successful candidates exhibited inhibitory activity with high affinity and selectivity toward COX-1. Three compounds were identified as leads for further development for PET imaging in monkeys.
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TARGETING PROTEIN−PROTEIN INTERACTIONS IN ALZHEIMER’S DISEASE
Significant research efforts and funding have been poured into the development of new drugs to treat Alzheimer’s disease (AD); despite this enormous concentration of resources, no new Alzheimer’s drugs have been successfully brought to market. One reason for this is the lack of a clear drug target: as drugs targeting amyloid-beta have repeatedly failed, new efforts are beginning to focus on other possible targets such as tau. Protein−protein interactions (PPIs) are also emerging as a new and promising class of drug targets. Here, Andrei and co-workers (DOI: 10.1021/acschemneuro.8b00118) explore PPIs as possible targets for the next generation of AD drugs. The authors propose targeting the PPI between 14-3-3 proteins, which bind to phosphorylated proteins, and tau protein, which binds and stabilizes microtubules in the brain. Tau interactions are regulated by phosphorylation, but hyperphosphorylation of tau is a hallmark of AD. The authors used NMR spectroscopy to characterize the binding of 14-3-3 to tau, identifying two high-affinity binding modes. They then designed a family of small molecules to inhibit this PPI as a means to further explore the role of this interaction in neurodegeneration.
A LASER FOCUS ON DEMENTIA
The two most common causes of dementia are Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). These two diseases share several symptoms and clinical characteristics, and misdiagnosis is common. To diagnose AD and DLB at the early stages, accurate tests for the appropriate biological markers must be developed. In recent years, blood biomarkers have emerged as a new avenue for detecting neurodegenerative diseases, as cerebrolspinal fluid is released into the bloodstream daily. Now, Paraskevaidi and co-workers (DOI: 10.1021/ acschemneuro.8b00198) explore chemical approaches for detecting and delineating AD and DLB at various stages of disease progression. Using Raman spectroscopy, the authors profiled blood plasma samples of 56 patients with DLB, early stage AD, and late-stage AD, and compared them to those of healthy individuals. By assigning wavenumbers to important biological molecules, the authors identified a panel of biomarkers distinguishing DLB from early- and late-stage AD, offering a cost-effective and minimally invasive diagnostic approach for dementia. © 2018 American Chemical Society
pubs.acs.org/chemneuro
Published: November 21, 2018 2520
DOI: 10.1021/acschemneuro.8b00612 ACS Chem. Neurosci. 2018, 9, 2520−2520
