Discovery of pentapeptide-inhibitor hits targeting FKBP51 by combining computational modeling and X-ray crystallography.

FKBP51 is well-known as a cochaperone of Hsp90 machinery and implicated in many human diseases including stress-related diseases, tau-mediated neurodegeneration and cancers, which makes FKBP51 an attractive drug target for the therapy of FKBP51-associated diseases. However, it has been reported that only nature product rapamycin, cyclosporine A, FK506 and its derivatives exhibit good binding affinities when bound to FKBP51 by now. Given the advantages of peptide-inhibitors, we designed and obtained 20 peptide-inhibitor hits through structure-based drug design.

Intranasal MMI-0100 Attenuates Aβ- and LPS-Induced Neuroinflammation and Memory Impairments via the MK2 Signaling Pathway.

Accumulating evidence suggests inhibiting neuroinflammation as a potential target in therapeutic or preventive strategies for Alzheimer's disease (AD). MAPK-activated protein kinase II (MK2), downstream kinase of p38 mitogen activated protein kinase (MAPK) p38 MAPK, was unveiled as a promising option for the treatment of AD. Increasing evidence points at MK2 as involved in neuroinflammatory responses.

The ventromedial hypothalamic nucleus plays an important role in anxiolytic-like effect of neuropeptide S.

Neuropeptide S (NPS), the endogenous neuropeptide ligand of NPSR, has been reported to regulate anxiety-related behavior involved in multiple brain regions, including amygdale, locus coeruleus and Barrington's nucleus. However, little research has been conducted on the anxiolytic-like behaviors of NPS on the hypothalamus, which was an important area in defensive behavior. Here, we investigated a role of hypothalamus in anxiolytic-like behaviors of NPS.