The results demonstrate alpha2 modulation of NMDA receptor function as an important mechanism for neuroprotection. These results suggest a new therapeutic approach based on neuromodulation, instead of direct inhibition, of the NMDA receptor for the treatment of glaucoma and other CNS disorders associated with NMDA receptor overactivation.

Oligodendrocytes (OLs) are the myelinating glia of the central nervous system. Injury to OLs causes myelin loss. In demyelinating diseases, such as multiple sclerosis, the remyelination is hindered principally due to a failure of the oligodendrocyte precursor cells (OPCs) to differentiate into mature OLs. To identify inducers of OPC to OL differentiation, a high‐throughput screening based on myelin basic protein expression using neural progenitor cells‐derived OPCs has been performed and, PD0325901—an MEK (MAPK kinase) inhibitor—is found to significantly enhance OPC to OL differentiation in a dose‐ and time‐dependent manner. Other MEK inhibitors also display similar effect, indicating blockade of MAPK–ERK signaling is sufficient to induce OPC differentiation into OLs. PD0325901 facilitates the formation of myelin sheaths in OPC–neuron co‐culture in vitro. And in experimental autoimmune encephalomyelitis model and cuprizone‐induced demyelination model, PD0325901 displays significant therapeutic effect by promoting myelin regeneration. Our results suggest that targeting the MAPK–ERK pathway might be an intriguing way to develop new therapies for demyelinating diseases.

Two new sarsolenane diterpenes, dihydrosarsolenone (2), methyl dihydrosarsolenoneate (3), and two new capnosane diterpenes, sarsolilides B (5) and C (6), were isolated together with the known analogue, sarsolilide A (4), from the Hainan soft coral Sarcophyton trocheliophorum Marenzeller. Their structures were elucidated by detailed spectroscopic analysis and by comparison with reported data, leading to a structure revision of sarsolenone (1). The absolute configurations of 2[a] State Key

Four new biscembranoids, bislatumlides C-F (1-4), were isolated from the Hainan soft coral Sarcophyton latum . Their structures were elucidated by detailed analysis of spectroscopic data and by comparison with reported data of related derivatives, leading to the structure revision of co-occurring bislatumlides A (5) and B (6) at the C-21 configuration. The absolute configurations of bislatumlides C and E (1 and 3) were determined by TDDFT calculations of their solution ECD spectra, allowing the configurational assignment of the related bislatumlides D and F (2 and 4) and A and B (5 and 6) as well. Bislatumlides A-F (1-6) represent the only biscembranoids formed by the undescribed coupling pattern of Diels-Alder cycloaddition between the Δ(1(2)) double bond involving an α,β-unsaturated γ-lactone ring as a dienophile group and a trisubstituted conjugated Δ(21(34))/Δ(35(36))-butadiene moiety. An endo-cycloaddition gave 1, 2, 5, and 6, whereas an exo-cycloaddition produced 3 and 4. This is the first report of exo-addition dicembranoids from marine sources and from nature. Bislatumlides C and E (1, 3) could be used as ECD reference compounds in the determination of absolute configuration for related derivatives.