Table 5.

Signal transduction pathways of acupuncture in treating Alzheimer's disease.

Subjects	Location	Acupoint	Intervention	Time of intervention	Signal pathway	Main results	Author, reference
Male, SD rat, scopolamine injection	brain	GV20	MA	pretreatment for 5 min, QD for 14 days	enhance cholinergic system-CREB-BDNF pathway	elevation of choline acetyltransferase, choline transporter 1, vesicular acetylcholine transporter, BDNF, CREB proteins neuroprotection	Lee B, et al. 2014[135]
APP/PS1 mice	brain	GV20	EA, 1/20 Hz	30min, QD for 4 weeks	modulation of BDNF-TrkB pathway	elevation of BDNF/proBDNF ratio, p-TrkB depression of β-amyloid (1-42), p75 anti-apoptosis	Lin R, et al. 2016[136]
Male, SAMP10	hippocampus	CV17, CV12, CV6, ST36, SP10	MA	QD	regulation of aging gene	elevation of p53, Mad related protein 2, Nucleoside diphosphate kinase B, AT motif-binding factor, Hsp84, Hsp86 depression of p38 MAPK, retinoblastoma-associated protein 1 anti-oxidation	Ding X, et al. 2006[18]
SD rat, Aβ1-40 injection	hippocampus, frontal cortex	GV20, KI3, ST36	EA, 1mA, 2Hz	15min, QD for 12 days	inactivation of p38 MAPK pathway	depression of p-p38 MAPK protein, IL-1beta mRNA decrease neuroinflammation	Fang JQ, et al. 2013[137]
Male, SD rat, Aβ1-40 injection	hippocampus CA1	GV20, BL23	EA, 2mA, 2-4V, 2Hz	20min, QD, 6 days/ wk for 4 weeks	activation of PPAR-γ pathway	elevation of PPAR-γ depression of p-p38MAPK, Aβ, p-Tau Ser404 protein decrease neuroinflammation	Zhang M, et al. 2017[138]
SAMP 10 mice	neocortex and hippocampus	CV17, CV12, CV6, SP10, ST36	not mentioned	QD for 14 days	p 130 pathway	elevation of p130 cell proliferation	Liu T, et al. 2008[139]
Male, SAMP8 mice	cortex and hippocampus	CV17, CV12, CV6, ST36, SP10	MA, >2Hz	30sec per acupoint, QD, 21 days	regulation of G protein/ IP3/ Ca2+ amplitude pathway	elevation of physiologically coupled activation rate and maximal coupled activation rate of Gαs and Gαi signal homeostasis	Luo B, et al. 2017[140]
Male, APP/PS1 mice	brain	GV20	EA, 1mA, 2/15Hz	30min, QD, 5 days/wk for 4 weeks	suppression of astrocytic NDRG2 pathway	depression of Glial fibrillary acidic protein, NDRG2 increase astrocytic reactivity	Wang F, et al. 2014[141]
telomerase-deficient mice(TERC-/-) mice	hippocampus and dentate gyrus	ST36	MA	30 min, QD for 4 days	activation of BDNF pathway	elevation of BDNF, TrkB, p75NTR, Akt, and ERK1/2 increase telomerase activity	Lin D, et al. 2015[142]
SD rat, beta-amyloid (Abeta)(1-40) injection	hippocampal	LI20, EX-HN3	EA, 1-3mA, 80-100Hz	10min, QD, 5 days/wk for 6 weeks	regulation of Bcl-2/Bax	elevation of Bcl-2 depression of Bax anti-apoptosis	Liu ZB, et al. 2011[143]
Male, SD rat, Aβ1-40 injection	hippocampus CA1	GV20, BL23	EA, <2mA, 20Hz	30 min, QD, 6 days/ wk for 4 weeks	downregulation of Notch pathway	elevation of Bcl-2, synapsin-1, synaptophysin depression of Bax, Notch1 mRNA, Hes1 mRNA anti-apoptosis	Guo HD, et al. 2015[144]
Male, APP/PS1 mice	hippocampus	GV20, KI1	EA, 1mA, 2/100Hz	15min, QD for 3 days	inactivation of caspase-3/ Bax pathway	elevation of Bcl-2/Bax ratio depression of caspase-3-positive cell number and Bax protein anti-apoptosis	Li XY, et al. 2016[145]
APP/PS1 mice	hippocampus, cortex	GV20	EA, 1/20Hz	30min, QD, 5 days/wk for 4 weeks	regulation of AMPK/mTOR pathway	elevation of GLUT1, GLUT3, p-AMPK, p-Akt, mTOR decrease Aβ (1-42) deposition, decrease autophagy process	Liu W, et al. 2017[148]
Male, SAMP8 mice	hippocampus CA1	GV14, BL23	EA, 1mA, 2Hz	20min, QD, 8 days' treatment and 2 days' rest for 3 cycles	activation of AMPK pathway	elevation of p-AMPK balance energy metabolism and improved cognitive impairment	Dong W, et al. 2015[20]
Male, SAMP8 mice	hippocampus and frontal cortex	GV14, BL23	EA, 1mA, 2Hz	20min, QD, 8 days' treatment and 2 days' rest for 3 cycles	activation of SIRT1-dependent PGC-1α expression pathway	elevation of ATP levels, SIRT1, PGC-1α depression of PGC-1α acetylation improved brain energy metabolism	Dong W, et al. 2015[151]

Abbreviations

Akt: protein kinase B; AMPK: AMP-activated protein kinase; APP/PS1: amyloid precursor protein (APP)/presenilin-1 (PS1) double transgenic; Bax: Bcl-2 associated X; Bcl-2: B-cell lymphoma 2; BDNF: brain-derived neurotrophic factor; CREB: phosphorylated cyclic AMP response element-binding protein; EA: electroacupuncture; ERK: extracellular signal-regulated kinase; GLUT: glucose transporter; IL: interleukin; IP3: Inositol triphosphate; MA: manual acupuncture; MAPK: mitogen-activated protein kinases; NDRG2: N-myc downregulated gene 2; NMDA: N-methyl-D-aspartate; PGC1: proliferator-activated receptor γ coactivator 1; PPAR-γ: peroxisome proliferator-activated receptors γ; QD: daily; QOD: every other day; RBL2: Retinoblastoma-like protein 2; SAMP: senescence-accelerated mouse prone; SD rat: Sprague Dawley rat; SIRT1: sirtuin 1; TrkB: tyrosine receptor kinase B.