Endoplasmic reticulum stress(ERS)is one of the major defense networks in mammals

but continuous ERS will lead to cell apoptosis

inducing initiation and progression of many human diseases.Biochemical

physiological and pathological stimuli induced ERS may help the cells adapt to and survive stress conditions by activating unfolded protein response(UPR)

ERoverload response and sterol modulation cascade reaction.Abundant outcomes of clinical and experimental studies in recent5 years showed that acupuncture and moxibustion therapies are effective in improving some symptoms of nervous system diseases as stroke

Parkinson's disease

convulsion

cardiovascular diseases

diabetes mellitus

non-alcoholic fatty liver disease

spinal cord injury

muscular injury

etc.

which is closely associated with their functions in relieving excessive ERS and cell apoptosis via modulating UPR pathway.Some important molecules or signaling pathways such as glucose-regulated protein 78(GRP78)

Caspase-12

ER transmembrane kinase inositol-requiring and ER-to-nucleus signaling protein(IRE1 P)

phosphorylated extracellular signal-regulated kinase(p-ERK)/eukaryotic translation initiation factor 2α(eIF2α)

activating transcription factor 4(ATF4)

CCAAT/enhancer-binding protein homologous protein(CHOP)

etc.have been demonstrated to be involved in the effects of acupuncture-moxibustion interventions.But

the mechanism of acupuncture-moxibustion underlying improvement of ERS remains far more unclear.Future studies targeting the combination of molecules and holistic function

verification of changes of the involved protein molecules and multiple signaling pathways

balancing regulation between the cell survival and apoptosis

etc.by adopting syndrome-differentiation-based acupoints are definitely needed.