In This Issue pubs.acs.org/chemneuro
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PROTECTING SENSORY NEURONS FROM CHEMOTHERAPY
may be used to treat cachexia or anorexia. To date, studies of melanocortin ligands have only been performed on male subjects. Here, Lensing et al. (DOI: 10.1021/acschemneuro.6b00156) examine the effects of antagonist compound SKY223-7 in both male and female mice. This work elucidates important sex differences of antagonist administration, where SKY2-23-7 increases food intake in both male and female mice, but at different doses. Additionally, males and females differed in energy expenditure rates, with females burning more calories per day at lower doses than males. It is posited that undesirable side effects of antagonist treatment that are observed in treatment of male patients may be less prominent in female patients. Consequently, melanocortin drugs exclusively targeting females may be a potential strategy to treat metabolic disorders.
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Chemotherapeutic cancer treatment may also harm noncancerous cells, including sensory neurons. As a result, chemotherapeutic-induced neuropathic pain (CINP) limits the use of these drugs in treating cancer. In this issue, Ma et al. (DOI: 10.1021/acschemneuro.6b00183) demonstrate that estrogen receptor beta selective agonists (ERβ agonists) successfully decrease neuropathic pain resulting from several classes of common chemotherapeutic agents. ERβ agonists were tested in male and female rats exhibiting neuropathy induced by the chemotherapeutics taxol, oxaliplatin, and vincristine. In addition to a marked reduction in neuropathic pain, this effect was shown to be specific to ERβ selective agonists, with ERα selective and nonselective estrogen agonists displaying no activity. Finally, the authors showed that ERβ selective agonists enhance the inhibitory effects of chemotherapeutic drugs in some cancer cell lines. These results show that ERβ agonists may be effective treatments for CINP.
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Aggregation of β-amyloid peptide (Aβ) into oligomers and fibrils is a hallmark of Alzheimer’s disease and is believed to cause neuronal death. Neurotoxicity may be prevented by employing compounds, such as peptides and peptide-related compounds, which selectively bind to Aβ and inhibit aggregation. In a unique approach, Lu et al. (DOI: 10.1021/ acschemneuro.6b00150) have designed peptides that mimic transthyretin (TTR), a neuroprotective protein that binds Aβ. In mimicking the Aβ-binding domain of TTR, Lu and coworkers rationally designed a family of cyclic peptides with systematic sequence changes using the TANGO algorithm. They synthesized and characterized these peptides to determine structure−activity relationships and identify enhanced performance relative to TTR. It was discovered that these cyclic peptides act through binding small Aβ aggregates, preventing further maturation and enabling degradation. These results represent an important advance in the development of novel defenses against Alzheimer’s disease.
SEX DIFFERENCES IN TUNING APPETITE IN MALE AND FEMALE MICE
The melanocortin system plays a critical role in energy homeostasis, and melanocortin ligands have been shown to affect appetite in humans and in mice. Melanocortin agonists decrease the desire to eat, making them a potential treatment for obesity, while antagonist compounds increase appetite and © 2016 American Chemical Society
FIGHTING ALZHEIMER’S DISEASE WITH SYNTHETIC PEPTIDES
Published: September 21, 2016 1177
DOI: 10.1021/acschemneuro.6b00283 ACS Chem. Neurosci. 2016, 7, 1177−1177
