PI3K/AKT signaling mediated by G protein‑coupled receptors is involved in neurodegenerative Parkinson's disease (Review)

Nakano,Noriko; Matsuda,Satoru; Ichimura,Mayuko; Minami,Akari; Ogino,Mako; Murai,Toshiyuki; Kitagishi,Yasuko

doi:10.3892/ijmm.2016.2833

PI3K/AKT signaling mediated by G protein‑coupled receptors is involved in neurodegenerative Parkinson's disease (Review)

Authors:
- Noriko Nakano
- Satoru Matsuda
- Mayuko Ichimura
- Akari Minami
- Mako Ogino
- Toshiyuki Murai
- Yasuko Kitagishi
View Affiliations

Affiliations: Department of Food Science and Nutrition, Nara Women's University, Kita‑Uoya Nishimachi, Nara 630‑8506, Japan, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita 565‑0871, Japan
Published online on: December 16, 2016 https://doi.org/10.3892/ijmm.2016.2833
Pages: 253-260

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Parkinson's disease (PD) is a common progressive and multifactorial neurodegenerative disease, characterized by the loss of midbrain dopaminergic neurons. Numerous pathological processes including, inflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalance, and apoptosis as well as genetic factors may lead to neuronal degeneration. Motor deficits in PD are due mostly to the progressive loss of nigrostriatal dopaminergic neurons. Neuroprotection of functional neurons is of significance in the treatment of PD. G protein‑coupled receptors (GPCRs) have been implicated in the neuroprotection against PD through the survival of dopaminergic neurons. In addition, phosphatidyl‑inositol‑3‑kinase (PI3K)/AKT signaling has also been demonstrated to be neuroprotective. Knowledge of the mechanisms involved in this cellular protection could be critical for developing treatments to prevent this neurodegenerative disorder. In this review, we highlight the protective roles of the PI3K/AKT signaling pathway in the function of representative serotonin GPCRs. Particular attention is given to the molecular mechanisms of this pathway proposed to explain the favorable effects of food ingredients against neurodegenerative disease.

View Figures

View References

1	Armento ME, Stanley MA, Marsh L, Kunik ME, York MK, Bush AL and Calleo JS: Cognitive behavioral therapy for depression and anxiety in Parkinson's disease: A clinical review. J Parkinsons Dis. 2:135–151. 2012.PubMed/NCBI
2	Jagmag SA, Tripathi N, Shukla SD, Maiti S and Khurana S: Evaluation of models of Parkinson's disease. Front Neurosci. 9:5032016. View Article : Google Scholar : PubMed/NCBI
3	Luo Y, Hoffer A, Hoffer B and Qi X: Mitochondria: A therapeutic target for Parkinson's disease? Int J Mol Sci. 16:20704–20730. 2015. View Article : Google Scholar : PubMed/NCBI
4	Giráldez-Pérez R, Antolín-Vallespín M, Muñoz M and Sánchez-Capelo A: Models of α-synuclein aggregation in Parkinson's disease. Acta Neuropathol Commun. 2:1762014. View Article : Google Scholar
5	Kim WS, Kågedal K and Halliday GM: Alpha-synuclein biology in Lewy body diseases. Alzheimers Res Ther. 6:732014. View Article : Google Scholar
6	Tokuhira N, Kitagishi Y, Suzuki M, Minami A, Nakanishi A, Ono Y, Kobayashi K, Matsuda S and Ogura Y: PI3K/AKT/PTEN pathway as a target for Crohn's disease therapy (Review). Int J Mol Med. 35:10–16. 2015.
7	Nakanishi A, Wada Y, Kitagishi Y and Matsuda S: Link between PI3K/AKT/PTEN pathway and NOX protein in diseases. Aging Dis. 5:203–211. 2014. View Article : Google Scholar : PubMed/NCBI
8	Huang JS, Cho CY, Hong CC, Yan MD, Hsieh MC, Lay JD, Lai GM, Cheng AL and Chuang SE: Oxidative stress enhances Axl-mediated cell migration through an Akt1/Rac1-dependent mechanism. Free Radic Biol Med. 65:1246–1256. 2013. View Article : Google Scholar : PubMed/NCBI
9	Luo H, Yang Y, Duan J, Wu P, Jiang Q and Xu C: PTEN-regulated AKT/FoxO3a/Bim signaling contributes to reactive oxygen species-mediated apoptosis in selenite-treated colorectal cancer cells. Cell Death Dis. 4:e4812013. View Article : Google Scholar : PubMed/NCBI
10	Maiese K, Chong ZZ, Wang S and Shang YC: Oxidant stress and signal transduction in the nervous system with the PI3-K, Akt, and mTOR cascade. Int J Mol Sci. 13:13830–13866. 2012. View Article : Google Scholar : PubMed/NCBI
11	Ma Y, Zhao P, Zhu J, Yan C, Li L, Zhang H, Zhang M, Gao X and Fan X: Naoxintong protects primary neurons from oxygen-glucose deprivation/reoxygenation induced injury through PI3K-Akt signaling pathway. Evid Based Complement Alternat Med. 2016:58159462016. View Article : Google Scholar : PubMed/NCBI
12	Flor PJ and Acher FC: Orthosteric versus allosteric GPCR activation: The great challenge of group-III mGluRs. Biochem Pharmacol. 84:414–424. 2012. View Article : Google Scholar : PubMed/NCBI
13	Bohn LM, Gainetdinov RR and Caron MG: G protein-coupled receptor kinase/beta-arrestin systems and drugs of abuse: Psychostimulant and opiate studies in knockout mice. Neuromolecular Med. 5:41–50. 2004. View Article : Google Scholar : PubMed/NCBI
14	Bhattacharya M, Babwah AV and Ferguson SS: Small GTP-binding protein-coupled receptors. Biochem Soc Trans. 32:1040–1044. 2004. View Article : Google Scholar : PubMed/NCBI
15	Lu CY, Yang YC, Li CC, Liu KL, Lii CK and Chen HW: Andrographolide inhibits TNFα-induced ICAM-1 expression via suppression of NADPH oxidase activation and induction of HO-1 and GCLM expression through the PI3K/Akt/Nrf2 and PI3K/Akt/AP-1 pathways in human endothelial cells. Biochem Pharmacol. 91:40–50. 2014. View Article : Google Scholar : PubMed/NCBI
16	Song S, Zhou F and Chen WR: Low-level laser therapy regulates microglial function through Src-mediated signaling pathways: Implications for neurodegenerative diseases. J Neuroinflammation. 9:2192012. View Article : Google Scholar : PubMed/NCBI
17	Akagi T, Murata K, Shishido T and Hanafusa H: v-Crk activates the phosphoinositide 3-kinase/AKT pathway by utilizing focal adhesion kinase and H-Ras. Mol Cell Biol. 22:7015–7023. 2002. View Article : Google Scholar : PubMed/NCBI
18	Ballou LM, Chattopadhyay M, Li Y, Scarlata S and Lin RZ: Galphaq binds to p110alpha/p85alpha phosphoinositide 3-kinase and displaces Ras. Biochem J. 394:557–562. 2006. View Article : Google Scholar :
19	Fritsch R, de Krijger I, Fritsch K, George R, Reason B, Kumar MS, Diefenbacher M, Stamp G and Downward J: Ras and Rho families of GTPases directly regulate distinct phosphoinositide 3-kinase isoforms. Cell. 153:1050–1063. 2013. View Article : Google Scholar : PubMed/NCBI
20	Dale LB, Bhattacharya M, Anborgh PH, Murdoch B, Bhatia M, Nakanishi S and Ferguson SS: G protein-coupled receptor kinase-mediated desensitization of metabotropic glutamate receptor 1A protects against cell death. J Biol Chem. 275:38213–38220. 2000. View Article : Google Scholar : PubMed/NCBI
21	Suire S, Lécureuil C, Anderson KE, Damoulakis G, Niewczas I, Davidson K, Guillou H, Pan D, Clark J, Stephens L and Hawkins PT: GPCR activation of Ras and PI3Kc in neutrophils depends on PLCβ2/β3 and the RasGEF RasGRP4. EMBO J. 31:3118–3129. 2012. View Article : Google Scholar : PubMed/NCBI
22	Xu CL, Wang JZ, Xia XP, Pan CW, Shao XX, Xia SL, Yang SX and Zheng B: Rab11-FIP2 promotes colorectal cancer migration and invasion by regulating PI3K/AKT/MMP7 signaling pathway. Biochem Biophys Res Commun. 470:397–404. 2016. View Article : Google Scholar : PubMed/NCBI
23	Shi GX, Cai W and Andres DA: Rit subfamily small GTPases: Regulators in neuronal differentiation and survival. Cell Signal. 25:2060–2068. 2013. View Article : Google Scholar : PubMed/NCBI
24	Julian L and Olson MF: Rho-associated coiled-coil containing kinases (ROCK): Structure, regulation, and functions. Small GTPases. 5:e298462014. View Article : Google Scholar : PubMed/NCBI
25	Uehara R, Hosoya H and Mabuchi I: In vivo phosphorylation of regulatory light chain of myosin II in sea urchin eggs and its role in controlling myosin localization and function during cytokinesis. Cell Motil Cytoskeleton. 65:100–115. 2008. View Article : Google Scholar
26	Koyanagi M, Takahashi J, Arakawa Y, Doi D, Fukuda H, Hayashi H, Narumiya S and Hashimoto N: Inhibition of the Rho/ROCK pathway reduces apoptosis during transplantation of embryonic stem cell-derived neural precursors. J Neurosci Res. 86:270–280. 2008. View Article : Google Scholar
27	Li G, Liu L, Shan C, Cheng Q, Budhraja A, Zhou T, Cui H and Gao N: RhoA/ROCK/PTEN signaling is involved in AT-101-mediated apoptosis in human leukemia cells in vitro and in vivo. Cell Death Dis. 5:e9982014. View Article : Google Scholar : PubMed/NCBI
28	Yang S and Kim HM: The RhoA-ROCK-PTEN pathway as a molecular switch for anchorage dependent cell behavior. Biomaterials. 33:2902–2915. 2012. View Article : Google Scholar : PubMed/NCBI
29	Song H and Gao D: Fasudil, a Rho-associated protein kinase inhibitor, attenuates retinal ischemia and reperfusion injury in rats. Int J Mol Med. 28:193–198. 2011.PubMed/NCBI
30	Man JH, Liang B, Gu YX, Zhou T, Li AL, Li T, Jin BF, Bai B, Zhang HY, Zhang WN, et al: Gankyrin plays an essential role in Ras-induced tumorigenesis through regulation of the RhoA/ROCK pathway in mammalian cells. J Clin Invest. 120:2829–2841. 2010. View Article : Google Scholar : PubMed/NCBI
31	Rodriguez-Viciana P, Warne PH, Dhand R, Vanhaesebroeck B, Gout I, Fry MJ, Waterfield MD and Downward J: Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature. 370:527–532. 1994. View Article : Google Scholar : PubMed/NCBI
32	Chu JM, Chen LW, Chan YS and Yung KK: Neuroprotective effects of neurokinin receptor one in dopaminergic neurons are mediated through Akt/PKB cell signaling pathway. Neuropharmacology. 61:1389–1398. 2011. View Article : Google Scholar : PubMed/NCBI
33	Saunders C, Siuta M, Robertson SD, Davis AR, Sauer J, Matthies HJ, Gresch PJ, Airey DC, Lindsley CW, Schetz JA, et al: Neuronal ablation of p-Akt at Ser473 leads to altered 5-HT1A/2A receptor function. Neurochem Int. 73:113–121. 2014. View Article : Google Scholar :
34	Dizeyi N, Hedlund P, Bjartell A, Tinzl M, Austild-Taskén K and Abrahamsson PA: Serotonin activates MAP kinase and PI3K/Akt signaling pathways in prostate cancer cell lines. Urol Oncol. 29:436–445. 2011. View Article : Google Scholar
35	Gil S, Park C, Lee J and Koh H: The roles of striatal serotonin and L-amino-acid decarboxylase on L-DOPA-induced dyskinesia in a hemiparkinsonian rat model. Cell Mol Neurobiol. 30:817–825. 2010. View Article : Google Scholar : PubMed/NCBI
36	Mazzucchi S, Frosini D, Ripoli A, Nicoletti V, Linsalata G, Bonuccelli U and Ceravolo R: Serotonergic antidepressant drugs and L-dopa-induced dyskinesias in Parkinson's disease. Acta Neurol Scand. 131:191–195. 2015.
37	Chan RJ, McBride AW and Crabb DW: Seven transmembrane domain receptor subtypes identified in NG108-15 cells by reverse transcription-polymerase chain reaction. Biochem Biophys Res Commun. 205:1311–1317. 1994. View Article : Google Scholar : PubMed/NCBI
38	González-Maeso J and Sealfon SC: Agonist-trafficking and hallucinogens. Curr Med Chem. 16:1017–1027. 2009. View Article : Google Scholar : PubMed/NCBI
39	Polter AM, Yang S, Jope RS and Li X: Functional significance of glycogen synthase kinase-3 regulation by serotonin. Cell Signal. 24:265–271. 2012. View Article : Google Scholar
40	Zamani A and Qu Z: Serotonin activates angiogenic phosphorylation signaling in human endothelial cells. FEBS Lett. 586:2360–2365. 2012. View Article : Google Scholar : PubMed/NCBI
41	Yin JA, Liu XJ, Yuan J, Jiang J and Cai SQ: Longevity manipulations differentially affect serotonin/dopamine level and behavioral deterioration in aging Caenorhabditis elegans. J Neurosci. 34:3947–3958. 2014. View Article : Google Scholar : PubMed/NCBI
42	Ivachtchenko AV and Ivanenkov YA: 5-HT(6) receptor antagonists: A patent update. Part 1. Sulfonyl derivatives. Expert Opin Ther Pat. 22:917–964. 2012. View Article : Google Scholar : PubMed/NCBI
43	Ponimaskin E, Voyno-Yasenetskaya T, Richter DW, Schachner M and Dityatev A: Morphogenic signaling in neurons via neurotransmitter receptors and small GTPases. Mol Neurobiol. 35:278–287. 2007. View Article : Google Scholar : PubMed/NCBI
44	Zhang G and Stackman RW Jr: The role of serotonin 5-HT2A receptors in memory and cognition. Front Pharmacol. 6:2252015. View Article : Google Scholar : PubMed/NCBI
45	Miguelez C, Morera-Herreras T, Torrecilla M, Ruiz-Ortega JA and Ugedo L: Interaction between the 5-HT system and the basal ganglia: Functional implication and therapeutic perspective in Parkinson's disease. Front Neural Circuits. 8:212014. View Article : Google Scholar : PubMed/NCBI
46	Cummings JL: Lewy body diseases with dementia: Pathophysiology and treatment. Brain Cogn. 28:266–280. 1995. View Article : Google Scholar : PubMed/NCBI
47	Monti JM: The role of dorsal raphe nucleus serotonergic and non-serotonergic neurons, and of their receptors, in regulating waking and rapid eye movement (REM) sleep. Sleep Med Rev. 14:319–327. 2010. View Article : Google Scholar : PubMed/NCBI
48	Monti JM and Jantos H: The roles of dopamine and serotonin, and of their receptors, in regulating sleep and waking. Prog Brain Res. 172:625–646. 2008. View Article : Google Scholar : PubMed/NCBI
49	Soiza-Reilly M and Commons KG: Quantitative analysis of glutamatergic innervation of the mouse dorsal raphe nucleus using array tomography. J Comp Neurol. 519:3802–3814. 2011. View Article : Google Scholar : PubMed/NCBI
50	Di Giovanni G, Esposito E and Di Matteo V: Role of serotonin in central dopamine dysfunction. CNS Neurosci Ther. 16:179–194. 2010. View Article : Google Scholar : PubMed/NCBI
51	Roussakis AA, Politis M, Towey D and Piccini P: Serotonin-to-dopamine transporter ratios in Parkinson disease: Relevance for dyskinesias. Neurology. 86:1152–1158. 2016. View Article : Google Scholar : PubMed/NCBI
52	Sekigawa A, Takamatsu Y, Sekiyama K and Hashimoto M: Role of α-and β-synucleins in the axonal pathology of Parkinson's disease and related synucleinopathies. Biomolecules. 5:1000–1011. 2015. View Article : Google Scholar : PubMed/NCBI
53	Buddhala C, Loftin SK, Kuley BM, Cairns NJ, Campbell MC, Perlmutter JS and Kotzbauer PT: Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease. Ann Clin Transl Neurol. 2:949–959. 2015. View Article : Google Scholar : PubMed/NCBI
54	Mace JL, Porter RJ, Dalrymple-Alford JC, Collins C and Anderson TJ: Acute tryptophan depletion and Lewy body dementias. Int Psychogeriatr. 28:1487–1491. 2016. View Article : Google Scholar : PubMed/NCBI
55	Peña E, Mata M, López-Manzanares L, Kurtis M, Eimil M, Martínez-Castrillo JC, Navas I, Posada IJ, Prieto C, Ruíz-Huete C, et al: Antidepressants in Parkinson's disease. Recommendations by the movement disorder study group of the Neurological Association of Madrid. Neurologia. Mar 19–2016.Epub ahead of print. PubMed/NCBI
56	Kim SR, Chen X, Oo TF, Kareva T, Yarygina O, Wang C, During M, Kholodilov N and Burke RE: Dopaminergic pathway reconstruction by Akt/Rheb-induced axon regeneration. Ann Neurol. 70:110–120. 2011. View Article : Google Scholar : PubMed/NCBI
57	Lin CH, Lin HI, Chen ML, Lai TT, Cao LP, Farrer MJ, Wu RM and Chien CT: Lovastatin protects neurite degeneration in LRRK2-G2019S parkinsonism through activating the Akt/Nrf pathway and inhibiting GSK3β activity. Hum Mol Genet. 25:1965–1978. 2016. View Article : Google Scholar : PubMed/NCBI
58	Cui Q, Li X and Zhu H: Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway. Mol Med Rep. 13:1381–1388. 2016.
59	Li X, Xie W, Xie C, Huang C, Zhu J, Liang Z, Deng F, Zhu M, Zhu W, Wu R, et al: Curcumin modulates miR-19/PTEN/AKT/p53 axis to suppress bisphenol A-induced MCF-7 breast cancer cell proliferation. Phytother Res. 28:1553–1560. 2014. View Article : Google Scholar : PubMed/NCBI
60	Yu W, Zha W, Ke Z, Min Q, Li C, Sun H and Liu C: Curcumin protects neonatal rat cardiomyocytes against high glucose-induced apoptosis via PI3K/Akt signalling pathway. J Diabetes Res. 2016:41585912016. View Article : Google Scholar : PubMed/NCBI
61	Chong CM, Zhou ZY, Razmovski-Naumovski V, Cui GZ, Zhang LQ, Sa F, Hoi PM, Chan K and Lee SM: Danshensu protects against 6-hydroxydopamine-induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish. Neurosci Lett. 543:121–125. 2013. View Article : Google Scholar : PubMed/NCBI
62	Zhu G, Wang X, Wu S, Li X and Li Q: Neuroprotective effects of puerarin on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced Parkinson's disease model in mice. Phytother Res. 28:179–186. 2014. View Article : Google Scholar
63	Bao XQ, Kong XC, Kong LB, Wu LY, Sun H and Zhang D: Squamosamide derivative FLZ protected dopaminergic neuron by activating Akt signaling pathway in 6-OHDA-induced in vivo and in vitro Parkinson's disease models. Brain Res. 1547:49–57. 2014. View Article : Google Scholar : PubMed/NCBI
64	Kwon SH, Ma SX, Hong SI, Kim SY, Lee SY and Jang CG: Eucommia ulmoides Oliv. bark attenuates 6-hydroxydopamine-induced neuronal cell death through inhibition of oxidative stress in SH-SY5Y cells. J Ethnopharmacol. 152:173–182. 2014. View Article : Google Scholar : PubMed/NCBI
65	Dewapriya P, Himaya SW, Li YX and Kim SK: Tyrosol exerts a protective effect against dopaminergic neuronal cell death in in vitro model of Parkinson's disease. Food Chem. 141:1147–1157. 2013. View Article : Google Scholar : PubMed/NCBI
66	Tasaki Y, Yamamoto J, Omura T, Sakaguchi T, Kimura N, Ohtaki K, Ono T, Suno M, Asari M, Ohkubo T, et al: Meloxicam ameliorates motor dysfunction and dopaminergic neurodegeneration by maintaining Akt-signaling in a mouse Parkinson's disease model. Neurosci Lett. 521:15–19. 2012. View Article : Google Scholar : PubMed/NCBI
67	Jin MC, Yoo JM, Sok DE and Kim MR: Neuroprotective effect of N-acetyl-5-hydroxytryptamines on glutamate-induced cytotoxicity in HT-22 cells. Neurochem Res. 39:2440–2451. 2014. View Article : Google Scholar : PubMed/NCBI
68	Ma J, Wang Z, Liu C, Shen H, Chen Z, Yin J, Zuo G, Duan X, Li H and Chen G: Pramipexole-induced hypothermia reduces early brain injury via PI3K/AKT/GSK3β pathway in subarachnoid hemorrhage rats. Sci Rep. 6:238172016. View Article : Google Scholar
69	Kuo HC, Chang HC, Lan WC, Tsai FH, Liao JC and Wu CR: Protective effects of Drynaria fortunei against 6-hydroxydopamine-induced oxidative damage in B35 cells via the PI3K/AKT pathway. Food Funct. 5:1956–1965. 2014. View Article : Google Scholar : PubMed/NCBI
70	Giuliani P, Ballerini P, Buccella S, Ciccarelli R, Rathbone MP, Romano S, D'Alimonte I, Caciagli F, Di Iorio P and Pokorski M: Guanosine protects glial cells against 6-hydroxydopamine toxicity. Adv Exp Med Biol. 837:23–33. 2015. View Article : Google Scholar
71	He Z, Chen AY, Rojanasakul Y, Rankin GO and Chen YC: Gallic acid, a phenolic compound, exerts anti-angiogenic effects via the PTEN/AKT/HIF-1α/VEGF signaling pathway in ovarian cancer cells. Oncol Rep. 35:291–297. 2016.
72	Caruso V, Le Grevés M, Shirazi Fard S, Haitina T, Olszewski PK, Alsiö J, Schiöth HB and Fredriksson R: The orphan G protein-coupled receptor gene GPR178 is evolutionary conserved and altered in response to acute changes in food intake. PLoS One. 10:e01220612015. View Article : Google Scholar : PubMed/NCBI
73	Guixà-González R, Javanainen M, Gómez-Soler M, Cordobilla B, Domingo JC, Sanz F, Pastor M, Ciruela F, Martinez-Seara H and Selent J: Membrane omega-3 fatty acids modulate the oligomerisation kinetics of adenosine A2A and dopamine D2 receptors. Sci Rep. 6:198392016. View Article : Google Scholar : PubMed/NCBI
74	Young G and Conquer J: Omega-3 fatty acids and neuropsychiatric disorders. Reprod Nutr Dev. 45:1–28. 2005. View Article : Google Scholar : PubMed/NCBI
75	Young GS, Conquer JA and Thomas R: Effect of randomized supplementation with high dose olive, flax or fish oil on serum phospholipid fatty acid levels in adults with attention deficit hyperactivity disorder. Reprod Nutr Dev. 45:549–558. 2005. View Article : Google Scholar : PubMed/NCBI
76	Yang RH, Lin J, Hou XH, Cao R, Yu F, Liu HQ, Ji AL, Xu XN, Zhang L and Wang F: Effect of docosahexaenoic acid on hippocampal neurons in high-glucose condition: Involvement of PI3K/AKT/nuclear factor-κB-mediated inflammatory pathways. Neuroscience. 274:218–228. 2014. View Article : Google Scholar : PubMed/NCBI
77	Simon BR, Parlee SD, Learman BS, Mori H, Scheller EL, Cawthorn WP, Ning X, Gallagher K, Tyrberg B, Assadi-Porter FM, et al: Artificial sweeteners stimulate adipogenesis and suppress lipolysis independently of sweet taste receptors. J Biol Chem. 288:32475–32489. 2013. View Article : Google Scholar : PubMed/NCBI
78	Huang W, Zhao Y, Zhu X, Cai Z, Wang S, Yao S, Qi Z and Xie P: Fluoxetine upregulates phosphorylated-AKT and phosphorylated-ERK1/2 proteins in neural stem cells: Evidence for a crosstalk between AKT and ERK1/2 pathways. J Mol Neurosci. 49:244–249. 2013. View Article : Google Scholar
79	Morandini L, Ramallo MR, Moreira RG, Höcht C, Somoza GM, Silva A and Pandolfi M: Serotonergic outcome, stress and sexual steroid hormones, and growth in a South American cichlid fish fed with an L-tryptophan enriched diet. Gen Comp Endocrinol. 223:27–37. 2015. View Article : Google Scholar : PubMed/NCBI
80	Seol GH, Shim HS, Kim PJ, Moon HK, Lee KH, Shim I, Suh SH and Min SS: Antidepressant-like effect of Salvia sclarea is explained by modulation of dopamine activities in rats. J Ethnopharmacol. 130:187–190. 2010. View Article : Google Scholar : PubMed/NCBI
81	Lee KB, Cho E and Kang YS: Changes in 5-hydroxytryptamine and cortisol plasma levels in menopausal women after inhalation of clary sage oil. Phytother Res. 28:1599–1605. 2014. View Article : Google Scholar : PubMed/NCBI
82	Qiu Y, Huang X, Huang L, Tang L, Jiang J, Chen L and Li S: 5-HT(1A) receptor antagonist improves behavior performance of delirium rats through inhibiting PI3K/Akt/mTOR activation-induced NLRP3 activity. IUBMB Life. 68:311–319. 2016. View Article : Google Scholar : PubMed/NCBI
83	Benmansour S, Privratsky AA, Adeniji OS and Frazer A: Signaling mechanisms involved in the acute effects of estradiol on 5-HT clearance. Int J Neuropsychopharmacol. 17:765–777. 2014. View Article : Google Scholar : PubMed/NCBI
84	Cui J, Shen Y and Li R: Estrogen synthesis and signaling pathways during aging: From periphery to brain. Trends Mol Med. 19:197–209. 2013. View Article : Google Scholar : PubMed/NCBI
85	Nakaso K, Tajima N, Horikoshi Y, Nakasone M, Hanaki T, Kamizaki K and Matsura T: The estrogen receptor β-PI3K/Akt pathway mediates the cytoprotective effects of tocotrienol in a cellular Parkinson's disease model. Biochim Biophys Acta. 1842:1303–1312. 2014. View Article : Google Scholar : PubMed/NCBI
86	Marwarha G, Rhen T, Schommer T and Ghribi O: The oxysterol 27-hydroxycholesterol regulates α-synuclein and tyrosine hydroxylase expression levels in human neuroblastoma cells through modulation of liver X receptors and estrogen receptors - relevance to Parkinson's disease. J Neurochem. 119:1119–1136. 2011. View Article : Google Scholar : PubMed/NCBI
87	Deusser J, Schmidt S, Ettle B, Plötz S, Huber S, Müller CP, Masliah E, Winkler J and Kohl Z: Serotonergic dysfunction in the A53T alpha-synuclein mouse model of Parkinson's disease. J Neurochem. 135:589–597. 2015. View Article : Google Scholar : PubMed/NCBI
88	Fazili NA and Naeem A: Anti-fibrillation potency of caffeic acid against an antidepressant induced fibrillogenesis of human α-synuclein: Implications for Parkinson's disease. Biochimie. 108:178–185. 2015. View Article : Google Scholar