TY - JOUR
T1 - 24(S)-Hydroxycholesterol as a Modulator of Neuronal Signaling and Survival
AU - Sun, Min Yu
AU - Linsenbardt, Andrew J.
AU - Emnett, Christine M.
AU - Eisenman, Lawrence N.
AU - Izumi, Yukitoshi
AU - Zorumski, Charles F.
AU - Mennerick, Steve
N1 - Publisher Copyright:
© SAGE Publications.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - The major cholesterol metabolite in brain, 24(S)-hydroxycholesterol (24S-HC), serves as a vehicle for cholesterol removal. Its effects on neuronal function, however, have only recently begun to be investigated. Here, we review that nascent work. Our own studies have demonstrated that 24S-HC has potent positive modulatory effects on N-methyl-d-aspartate (NMDA) receptor (NMDAR) function. This could have implications not only for brain plasticity but also for pathological NMDAR overuse. Other work has demonstrated effects of 24S-HC on neuronal survival and as a possible biomarker of neurodegenerative disease. Depending on circumstances, both upregulation/mimicry of 24S-HC signaling and down-regulation/antagonism may have therapeutic potential. We are interested in the possibility that synthetic analogues of 24S-HC with positive effects at NMDARs may hold neurotherapeutic promise, given the role of NMDA receptor hypofunction in certain neuropsychiatric disorders.
AB - The major cholesterol metabolite in brain, 24(S)-hydroxycholesterol (24S-HC), serves as a vehicle for cholesterol removal. Its effects on neuronal function, however, have only recently begun to be investigated. Here, we review that nascent work. Our own studies have demonstrated that 24S-HC has potent positive modulatory effects on N-methyl-d-aspartate (NMDA) receptor (NMDAR) function. This could have implications not only for brain plasticity but also for pathological NMDAR overuse. Other work has demonstrated effects of 24S-HC on neuronal survival and as a possible biomarker of neurodegenerative disease. Depending on circumstances, both upregulation/mimicry of 24S-HC signaling and down-regulation/antagonism may have therapeutic potential. We are interested in the possibility that synthetic analogues of 24S-HC with positive effects at NMDARs may hold neurotherapeutic promise, given the role of NMDA receptor hypofunction in certain neuropsychiatric disorders.
KW - Alzheimer's disease
KW - NMDA
KW - apoptosis
KW - cholesterol. 24(S)-hydroxycholesterol
KW - glutamate
UR - http://www.scopus.com/inward/record.url?scp=84962598388&partnerID=8YFLogxK
U2 - 10.1177/1073858414568122
DO - 10.1177/1073858414568122
M3 - Review article
C2 - 25628343
AN - SCOPUS:84962598388
SN - 1073-8584
VL - 22
SP - 132
EP - 144
JO - Neuroscientist
JF - Neuroscientist
IS - 2
ER -