Food-derived Peptides as Promising Neuroprotective Agents: Mechanism
and Therapeutic Potential

Kavita      Patel; Ashutosh      Mani
Abstract

Many food-derived peptides have the potential to improve brain health and slow down neurodegeneration. Peptides are produced by the enzymatic hydrolysis of proteins from different food sources. These peptides have been shown to be involved in antioxidant and anti-inflammatory activity, neuro-transmission modulation, and gene expression regulation. Although few peptides directly affect chromatin remodeling and histone alterations, others indirectly affect the neuroprotection process by interfering with epigenetic changes. Fish-derived peptides have shown neuroprotective properties that reduce oxidative stress and improve motor dysfunction in Parkinson's disease models. Peptides from milk and eggs have been found to have anti-inflammatory properties that reduce inflammation and improve cognitive function in Alzheimer's disease models. These peptides are potential therapeutics for neurodegenerative diseases, but more study is required to assess their efficacy and the underlying neuroprotective benefits. Consequently, this review concentrated on each mechanism of action used by food-derived peptides that have neuroprotective advantages and applications in treating neurodegenerative diseases. This article highlights various pathways, such as inflammatory pathways, major oxidant pathways, apoptotic pathways, neurotransmitter modulation, and gene regulation through which food-derived peptides interact at the cellular level.
Graphical Abstract

[1]
Galland, F.; de Espindola, J.S.; Lopes, D.S.; Taccola, M.F.; Pacheco, M.T.B. Food-derived bioactive peptides: Mechanisms of action underlying inflammation and oxidative stress in the central nervous system. Food Chemist. Adv.,  2022, 1, 100087.
 [http://dx.doi.org/10.1016/j.focha.2022.100087]

[2]
Andersen, J.K. Oxidative stress in neurodegeneration: Cause or consequence? Nat. Med.,  2004, 10(S7), S18-S25.
 [http://dx.doi.org/10.1038/nrn1434] [PMID: 15298006]

[3]
Sahin, E.; DePinho, R.A. Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature,  2010, 464(7288), 520-528.
 [http://dx.doi.org/10.1038/nature08982] [PMID: 20336134]

[4]
Chakrabarti, S.; Jahandideh, F.; Wu, J. Food-derived bioactive peptides on inflammation and oxidative stress. BioMed Res. Int.,  2014, 2014

[5]
Wang, S.; Waterhouse, S.D.; Waterhouse, N.G.I.; Zheng, L.; Su, G.; Zhao, M. Effects of food-derived bioactive peptides on cognitive deficits and memory decline in neurodegenerative diseases: A review. Trends Food Sci. Technol.,  2021, 116, 712-732.
 [http://dx.doi.org/10.1016/j.tifs.2021.04.056]

[6]
Tortarolo, M.; Veglianese, P.; Calvaresi, N.; Botturi, A.; Rossi, C.; Giorgini, A.; Migheli, A.; Bendotti, C. Persistent activation of p38 mitogen-activated protein kinase in a mouse model of familial amyotrophic lateral sclerosis correlates with disease progression. Mol. Cell. Neurosci.,  2003, 23(2), 180-192.
 [http://dx.doi.org/10.1016/S1044-7431(03)00022-8] [PMID: 12812752]

[7]
Trivedi, M.S.; Shah, J.S.; Al-Mughairy, S.; Hodgson, N.W.; Simms, B.; Trooskens, G.A.; Van Criekinge, W.; Deth, R.C. Food-derived opioid peptides inhibit cysteine uptake with redox and epigenetic consequences. J. Nutr. Biochem.,  2014, 25(10), 1011-1018.
 [http://dx.doi.org/10.1016/j.jnutbio.2014.05.004] [PMID: 25018147]

[8]
Guha, S.; Majumder, K. Structural-features of food-derived bioactive peptides with anti-inflammatory activity: A brief review. J. Food Biochem.,  2019, 43(1), e12531.
 [http://dx.doi.org/10.1111/jfbc.12531] [PMID: 31353488]

[9]
Min, L.J.; Kobayashi, Y.; Mogi, M.; Tsukuda, K.; Yamada, A.; Yamauchi, K.; Abe, F.; Iwanami, J.; Xiao, J.Z.; Horiuchi, M. Administration of bovine casein-derived peptide prevents cognitive decline in Alzheimer disease model mice. PLoS One,  2017, 12(2), e0171515.
 [http://dx.doi.org/10.1371/journal.pone.0171515] [PMID: 28158298]

[10]
Perlikowska, R. Whether short peptides are good candidates for future neuroprotective therapeutics? Peptides,  2021, 140, 170528.
 [http://dx.doi.org/10.1016/j.peptides.2021.170528] [PMID: 33716091]

[11]
Mason, J.M. Design and development of peptides and peptide mimetics as antagonists for therapeutic intervention. Future Med. Chem.,  2010, 2(12), 1813-1822.
 [http://dx.doi.org/10.4155/fmc.10.259] [PMID: 21428804]

[12]
Smith, D.E.; Clémençon, B.; Hediger, M.A. Proton-coupled oligopeptide transporter family SLC15: Physiological, pharmacological and pathological implications. Mol. Aspects Med.,  2013, 34(2-3), 323-336.
 [http://dx.doi.org/10.1016/j.mam.2012.11.003] [PMID: 23506874]

[13]
Xu, Q.; Yan, X.; Zhang, Y.; Wu, J. Current understanding of transport and bioavailability of bioactive peptides derived from dairy proteins: A review. Int. J. Food Sci. Technol.,  2019, 54(6), 1930-1941.
 [http://dx.doi.org/10.1111/ijfs.14055]

[14]
Banks, W.A. From blood–brain barrier to blood–brain interface: New opportunities for CNS drug delivery. Nat. Rev. Drug Discov.,  2016, 15(4), 275-292.
 [http://dx.doi.org/10.1038/nrd.2015.21] [PMID: 26794270]

[15]
Tanaka, M.; Dohgu, S.; Komabayashi, G.; Kiyohara, H.; Takata, F.; Kataoka, Y.; Nirasawa, T.; Maebuchi, M.; Matsui, T. Brain- transportable dipeptides across the blood-brain barrier in mice. Sci. Rep.,  2019, 9(1), 5769.
 [http://dx.doi.org/10.1038/s41598-019-42099-9] [PMID: 30962462]

[16]
Matsui, T.; Yoshino, A.; Tanaka, M. A trip of peptides to the brain. Food Prod. Process. Nutr.,  2020, 2(1), 30.
 [http://dx.doi.org/10.1186/s43014-020-00044-8]

[17]
Guidotti, G.; Brambilla, L.; Rossi, D. Cell-penetrating peptides: From basic research to clinics. Trends Pharmacol. Sci.,  2017, 38(4), 406-424.
 [http://dx.doi.org/10.1016/j.tips.2017.01.003] [PMID: 28209404]

[18]
Kigerl, K.A.; de Vaccari, R.J.P.; Dietrich, W.D.; Popovich, P.G.; Keane, R.W. Pattern recognition receptors and central nervous system repair. Exp. Neurol.,  2014, 258, 5-16.
 [http://dx.doi.org/10.1016/j.expneurol.2014.01.001] [PMID: 25017883]

[19]
Glass, C.K.; Saijo, K.; Winner, B.; Marchetto, M.C.; Gage, F.H. Mechanisms underlying inflammation in neurodegeneration. Cell,  2010, 140(6), 918-934.
 [http://dx.doi.org/10.1016/j.cell.2010.02.016] [PMID: 20303880]

[20]
Shabab, T.; Khanabdali, R.; Moghadamtousi, S.Z.; Kadir, H.A.; Mohan, G. Neuroinflammation pathways: A general review. Int. J. Neurosci.,  2017, 127(7), 624-633.
 [http://dx.doi.org/10.1080/00207454.2016.1212854] [PMID: 27412492]

[21]
Kim, G.H.; Kim, J.E.; Rhie, S.J.; Yoon, S. The role of oxidative stress in neurodegenerative diseases. Exp. Neurobiol.,  2015, 24(4), 325-340.
 [http://dx.doi.org/10.5607/en.2015.24.4.325] [PMID: 26713080]

[22]
Niedzielska, E.; Smaga, I.; Gawlik, M.; Moniczewski, A.; Stankowicz, P.; Pera, J.; Filip, M. Oxidative stress in neurodegenerative diseases. Mol. Neurobiol.,  2016, 53(6), 4094-4125.
 [http://dx.doi.org/10.1007/s12035-015-9337-5] [PMID: 26198567]

[23]
Zou, T.-B.; He, T.-P.; Li, H.-B.; Tang, H.-W.; Xia, E.-Q. The structure-activity relationship of the antioxidant peptides from natural proteins. Molecules,  2016, 21, 72.
 [http://dx.doi.org/10.3390/molecules21010072]

[24]
Sarmadi, B.H.; Ismail, A. Antioxidative peptides from food proteins: A review. Peptides,  2010, 31(10), 1949-1956.
 [http://dx.doi.org/10.1016/j.peptides.2010.06.020] [PMID: 20600423]

[25]
Hajji, N.; Calvert, C.; Ritchie, C.; Sastre, M. The role of metals in alzheimer’s disease. In: Metallobiology; Royal Society Of Chemistry, 2013; pp. 978-1.
 [http://dx.doi.org/10.1039/9781849735896-00080]

[26]
Amakye, W.K.; Hou, C.; Xie, L.; Lin, X.; Gou, N.; Yuan, E.; Ren, J. Bioactive anti-aging agents and the identification of new anti-oxidant soybean peptides. Food Biosci.,  2021, 42, 101194.
 [http://dx.doi.org/10.1016/j.fbio.2021.101194]

[27]
Zhu, K.X.; Guo, X.; Guo, X.N.; Peng, W.; Zhou, H.M. Protective effects of wheat germ protein isolate hydrolysates (WGPIH) against hydrogen peroxide-induced oxidative stress in PC12 cells. Food Res. Int.,  2013, 53(1), 297-303.
 [http://dx.doi.org/10.1016/j.foodres.2013.05.007]

[28]
Chen, H.; Zhao, M.; Lin, L.; Wang, J.; Sun-Waterhouse, D.; Dong, Y.; Zhuang, M.; Su, G. Identification of antioxidative peptides from defatted walnut meal hydrolysate with potential for improving learning and memory. Food Res. Int.,  2015, 78, 216-223.
 [http://dx.doi.org/10.1016/j.foodres.2015.10.008] [PMID: 28433285]

[29]
Caetano-Silva, M.E.; Rund, L.A.; Vailati-Riboni, M.; Pacheco, M.T.B.; Johnson, R.W. Copper-binding peptides attenuate microglia inflammation through suppression of NF-kB pathway. Mol. Nutr. Food Res.,  2021, 65(22), 2100153.
 [http://dx.doi.org/10.1002/mnfr.202100153] [PMID: 34532985]

[30]
Gao, Y.; Qin, H.; Wu, D.; Liu, C.; Fang, L.; Wang, J.; Liu, X.; Min, W. Walnut peptide WEKPPVSH in allevia
            ting oxidative stress and inflammation in lipopolysaccharide-activated BV-2 microglia via the Nrf2/HO-1 and NF-κB/p38 MAPK pathways. J. Biosci. Bioeng.,  2021, 132(5), 496-504.
 [http://dx.doi.org/10.1016/j.jbiosc.2021.07.009] [PMID: 34509368]

[31]
Yu, T.; Guo, J.; Zhu, S.; Zhang, X.; Zhu, Z.Z.; Cheng, S.; Cong, X. Protective effects of selenium-enriched peptides from Cardamine violifolia on d-galactose-induced brain aging by alleviating oxidative stress, neuroinflammation, and neuron apoptosis. J. Funct. Foods,  2020, 75, 104277.
 [http://dx.doi.org/10.1016/j.jff.2020.104277]

[32]
Zhang, J.; Liu, R.; Zhang, D.; Zhang, Z.; Zhu, J.; Xu, L.; Guo, Y. Neuroprotective effects of maize tetrapeptide-anchored gold nanoparticles in Alzheimer’s disease. Colloids Surf. B Biointerfaces,  2021, 200, 111584.
 [http://dx.doi.org/10.1016/j.colsurfb.2021.111584] [PMID: 33508658]

[33]
Zhao, F.; Liu, C.; Fang, L.; Lu, H.; Wang, J.; Gao, Y.; Gabbianelli, R.; Min, W. Walnut-derived peptide activates PINK1 via the NRF2/KEAP1/HO-1 pathway, promotes mitophagy, and alleviates learning and memory impairments in a mice model. J. Agric. Food Chem.,  2021, 69(9), 2758-2772.
 [http://dx.doi.org/10.1021/acs.jafc.0c07546] [PMID: 33591165]

[34]
Michalska, P.; León, R. When it comes to an end: Oxidative stress crosstalk with protein aggregation and neuroinflammation induce neurodegeneration. Antioxidants,  2020, 9(8), 740.
 [http://dx.doi.org/10.3390/antiox9080740] [PMID: 32806679]

[35]
Chai, H.J.; Chan, Y.L.; Li, T.L.; Shiau, C.Y.; Wu, C.J. Evaluation of lanternfish (Benthosema pterotum) hydrolysates as antioxidants against hydrogen peroxide induced oxidative injury. Food Res. Int.,  2013, 54(2), 1409-1418.
 [http://dx.doi.org/10.1016/j.foodres.2013.09.052]

[36]
Zou, Y.; Feng, W.; Wang, W.; Chen, Y.; Zhou, Z.; Li, Q.; Zhao, T.; Mao, G.; Wu, X.; Yang, L. Protective effect of porcine cerebral hydrolysate peptides on learning and memory deficits and oxidative stress in lead-exposed mice. Biol. Trace Elem. Res.,  2015, 168(2), 429-440.
 [http://dx.doi.org/10.1007/s12011-015-0329-0] [PMID: 25956150]

[37]
Miao, M.; Yu, W.Q.; Li, Y.; Sun, Y.L.; Guo, S.D. Structural elucidation and activities of Cordyceps militaris-derived polysaccharides: A review. Front. Nutr.,  2022, 9, 898674.
 [http://dx.doi.org/10.3389/fnut.2022.898674] [PMID: 35711557]

[38]
Ciesielska, A.; Matyjek, M.; Kwiatkowska, K. TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cell. Mol. Life Sci.,  2021, 78(4), 1233-1261.
 [http://dx.doi.org/10.1007/s00018-020-03656-y] [PMID: 33057840]

[39]
Zhu, G.P.; Zhang, C.H.; Qin, X.M.; Cao, W.H.; Zheng, H.N.; Gao, J.L. Ameliorative effects of oyster (Crassostrea hongkongensis) protein hydrolysate on age-induced cognitive impairment via restoring glia cell dysfunction and neuronal injured in zebrafish. J. Funct. Foods,  2021, 85, 104607.
 [http://dx.doi.org/10.1016/j.jff.2021.104607]

[40]
Wang, X.; Yu, H.; Xing, R.; Liu, S.; Chen, X.; Li, P. Effect and mechanism of oyster hydrolytic peptides on spatial learning and memory in mice. RSC Advances,  2018, 8(11), 6125-6135.
 [http://dx.doi.org/10.1039/C7RA13139A] [PMID: 35539616]

[41]
Kaminska, B. MAPK signalling pathways as molecular targets for anti-inflammatory therapy—From molecular mechanisms to therapeutic benefits. Biochim. Biophys. Acta BBA - Prot. Proteom.,  2005, 1754, 253-262.
 [http://dx.doi.org/10.1016/j.bbapap.2005.08.017]

[42]
Takeuchi, O.; Akira, S. Pattern recognition receptors and inflammation. Cell,  2010, 140(6), 805-820.
 [http://dx.doi.org/10.1016/j.cell.2010.01.022] [PMID: 20303872]

[43]
Corpuz, H.M.; Fujii, H.; Nakamura, S.; Katayama, S. Fermented rice peptides attenuate scopolamine-induced memory impairment in mice by regulating neurotrophic signaling pathways in the hippocampus. Brain Res,  2019, 1720, 146322.
 [http://dx.doi.org/10.1016/j.brainres.2019.146322]

[44]
Liang, Y.; Lin, Q.; Huang, P.; Wang, Y.; Li, J.; Zhang, L.; Cao, J. Rice bioactive peptide binding with TLR4 To Overcome H 2 O 2 -induced injury in human umbilical vein endothelial cells through nf-κb signaling. J. Agric. Food Chem.,  2018, 66(2), 440-448.
 [http://dx.doi.org/10.1021/acs.jafc.7b04036] [PMID: 29276944]

[45]
Ko, W.; Sohn, J.H.; Jang, J.H.; Ahn, J.S.; Kang, D.G.; Lee, H.S.; Kim, J.S.; Kim, Y.C.; Oh, H. Inhibitory effects of alternaramide on inflammatory mediator expression through TLR4-MyD88-mediated inhibition of NF-кB and MAPK pathway signaling in lipopolysaccharide-stimulated RAW264.7 and BV2 cells. Chem. Biol. Interact.,  2016, 244, 16-26.
 [http://dx.doi.org/10.1016/j.cbi.2015.11.024] [PMID: 26620692]

[46]
Chataigner, M.; Martin, M.; Lucas, C.; Pallet, V.; Layé, S.; Mehaignerie, A.; Bouvret, E.; Dinel, A.L.; Joffre, C. Fish hydrolysate supplementation containing n-3 long chain polyunsaturated fatty acids and peptides prevents LPS-induced neuroinflammation. Nutrients,  2021, 13(3), 824.
 [http://dx.doi.org/10.3390/nu13030824] [PMID: 33801489]

[47]
Wang, Y.; Xu, E.; Musich, P.R.; Lin, F. Mitochondrial dysfunction in neurodegenerative diseases and the potential countermeasure. CNS Neurosci. Ther.,  2019, 25(7), 816-824.
 [http://dx.doi.org/10.1111/cns.13116] [PMID: 30889315]

[48]
Bauer, T.M.; Murphy, E. Role of mitochondrial calcium and the permeability transition pore in regulating cell death. Circ. Res.,  2020, 126(2), 280-293.
 [http://dx.doi.org/10.1161/CIRCRESAHA.119.316306] [PMID: 31944918]

[49]
Wang, S.; Su, G.; Zhang, Q.; Zhao, T.; Liu, Y.; Zheng, L.; Zhao, M. Walnut ( Juglans regia ) peptides reverse sleep deprivation-induced memory impairment in rat via alleviating oxidative stress. J. Agric. Food Chem.,  2018, 66(40), 10617-10627.
 [http://dx.doi.org/10.1021/acs.jafc.8b03884] [PMID: 30226056]

[50]
Ren, D.; Zhao, F.; Liu, C.; Wang, J.; Guo, Y.; Liu, J.; Min, W. Antioxidant hydrolyzed peptides from Manchurian walnut ( Juglans mandshurica Maxim.) attenuate scopolamine-induced memory impairment in mice. J. Sci. Food Agric.,  2018, 98(13), 5142-5152.
 [http://dx.doi.org/10.1002/jsfa.9060] [PMID: 29652442]

[51]
Kriete, A.; Mayo, K.L. Atypical pathways of NF-κB activation and aging. Exp. Gerontol.,  2009, 44(4), 250-255.
 [http://dx.doi.org/10.1016/j.exger.2008.12.005] [PMID: 19174186]

[52]
Kim, E.K.; Lee, S-J.; Moon, S-H.; Jeon, B-T.; Kim, B.; Park, T-K.; Han, J-S.; Park, P-J. Neuroprotective effects of a novel peptide purified from venison protein. J. Microbiol. Biotechnol.,  2010, 20(4), 700-707.
 [http://dx.doi.org/10.4014/jmb.0909.09033] [PMID: 20467241]

[53]
Wang, S.; Zheng, L.; Zhao, T.; Zhang, Q.; Su, G.; Zhao, M. The neuroprotective effect of walnut-derived peptides against glutamate-induced damage in PC12 cells: Mechanism and bioavailability. Food Sci. Hum. Wellness,  2022, 11(4), 933-942.
 [http://dx.doi.org/10.1016/j.fshw.2022.03.021]

[54]
Xu, Z.; Chen, S.; Wang, Y.; Chen, S.; Yao, W.; Gao, X. Neuroprotective effects of silk fibroin hydrolysate against Aβ25–35 induced cytotoxicity in SH-SY5Y cells and primary hippocampal neurons by regulating ROS inactivation of PP2A. J. Funct. Foods,  2018, 45, 100-109.
 [http://dx.doi.org/10.1016/j.jff.2018.03.032]

[55]
Zhao, Y.; Dong, Y.; Ge, Q.; Cui, P.; Sun, N.; Lin, S. Neuroprotective effects of NDEELNK from sea cucumber ovum against scopolamine-induced PC12 cell damage through enhancing energy metabolism and upregulation of the PKA/BDNF/NGF signaling pathway. Food Funct.,  2021, 12(17), 7676-7687.
 [http://dx.doi.org/10.1039/D1FO00631B] [PMID: 34259275]

[56]
Lemus-Conejo, A.; Millan-Linares, M.C.; Toscano, R.; Millan, F.; Pedroche, J.; Muriana, F.J.G.; Montserrat-de la Paz, S. GPETAFLR, a peptide from lupinus angustifolius L. prevents inflammation in microglial cells and confers neuroprotection in brain. Nutr. Neurosci.,  2022, 25(3), 472-484.
 [http://dx.doi.org/10.1080/1028415X.2020.1763058] [PMID: 32401697]

[57]
Fang, Y.; Xu, Z.; Shi, Y.; Pei, F.; Yang, W.; Ma, N.; Kimatu, B.M.; Liu, K.; Qiu, W.; Hu, Q. Protection mechanism of Se-containing protein hydrolysates from Se-enriched rice on Pb2+-induced apoptosis in PC12 and RAW264.7 cells. Food Chem.,  2017, 219, 391-398.
 [http://dx.doi.org/10.1016/j.foodchem.2016.09.131] [PMID: 27765242]

[58]
Pei, X.; Yang, R.; Zhang, Z.; Gao, L.; Wang, J.; Xu, Y.; Zhao, M.; Han, X.; Liu, Z.; Li, Y. Marine collagen peptide isolated from Chum Salmon (Oncorhynchus keta) skin facilitates learning and memory in aged C57BL/6J mice. Food Chem.,  2010, 118(2), 333-340.
 [http://dx.doi.org/10.1016/j.foodchem.2009.04.120]

[59]
Zhao, T.; Zheng, L.; Zhang, Q.; Wang, S.; Zhao, Q.; Su, G.; Zhao, M. Stability towards the gastrointestinal simulated digestion and bioactivity of PAYCS and its digestive product PAY with cognitive improving properties. Food Funct.,  2019, 10(5), 2439-2449.
 [http://dx.doi.org/10.1039/C8FO02314J] [PMID: 30968880]

[60]
Yu, Z.; Ji, H.; Shen, J.; Kan, R.; Zhao, W.; Li, J.; Ding, L.; Liu, J. Identification and molecular docking study of fish roe-derived peptides as potent BACE 1, AChE, and BChE inhibitors. Food Funct.,  2020, 11(7), 6643-6651.
 [http://dx.doi.org/10.1039/D0FO00971G] [PMID: 32656560]

[61]
Lu, M.; Mishra, A.; Boschetti, C.; Lin, J.; Liu, Y.; Huang, H.; Kaminski, C.F.; Huang, Z.; Tunnacliffe, A.; Schierle, K.G.S. Sea cucumber-derived peptides alleviate oxidative stress in neuroblastoma cells and improve survival in C. elegans exposed to neurotoxic paraquat. Oxid. Med. Cell. Longev.,  2021, 2021, 1-14.
 [http://dx.doi.org/10.1155/2021/8842926] [PMID: 33959216]

[62]
Ano, Y.; Ayabe, T.; Kutsukake, T.; Ohya, R.; Takaichi, Y.; Uchida, S.; Yamada, K.; Uchida, K.; Takashima, A.; Nakayama, H. Novel lactopeptides in fermented dairy products improve memory function and cognitive decline. Neurobiol. Aging,  2018, 72, 23-31.
 [http://dx.doi.org/10.1016/j.neurobiolaging.2018.07.016] [PMID: 30176402]

[63]
Dobransky, T.; Rylett, J.R. Functional regulation of choline acetyltransferase by phosphorylation. Neurochem. Res.,  2003, 28(3/4), 537-542.
 [http://dx.doi.org/10.1023/A:1022873323561] [PMID: 12675142]

[64]
Lin, L.; Yang, K.; Zheng, L.; Zhao, M.; Sun, W.; Zhu, Q.; Liu, S. Anti-aging effect of sea cucumber (Cucumaria frondosa) hydrolysate on fruit flies and d-galactose-induced aging mice. J. Funct. Foods,  2018, 47, 11-18.
 [http://dx.doi.org/10.1016/j.jff.2018.05.033]

[65]
Grifman, M.; Arbel, A.; Ginzberg, D.; Glick, D.; Elgavish, S.; Shaanan, B.; Soreq, H. in vitro phosphorylation of acetylcholinesterase at non-consensus protein kinase A sites enhances the rate of acetylcholine hydrolysis. Brain Res. Mol. Brain Res.,  1997, 51(1-2), 179-187.
 [http://dx.doi.org/10.1016/S0169-328X(97)00246-5] [PMID: 9427520]

[66]
Biggins, J.B.; Gleber, C.D.; Brady, S.F. Acyldepsipeptide HDAC inhibitor production induced in Burkholderia thailandensis. Org. Lett.,  2011, 13(6), 1536-1539.
 [http://dx.doi.org/10.1021/ol200225v] [PMID: 21348454]

[67]
Harrison, S.J.; Bishton, M.; Bates, S.E.; Grant, S.; Piekarz, R.L.; Johnstone, R.W.; Dai, Y.; Lee, B.; Araujo, M.E.; Prince, H.M. A focus on the preclinical development and clinical status of the histone deacetylase inhibitor, romidepsin (depsipeptide, Istodax ® ). Epigenomics,  2012, 4(5), 571-589.
 [http://dx.doi.org/10.2217/epi.12.52] [PMID: 23130838]

[68]
Wan, X.; Liu, H.; Sun, Y.; Zhang, J.; Chen, X.; Chen, N. Lunasin: A promising polypeptide for the prevention and treatment of cancer. Oncol. Lett.,  2017, 13(6), 3997-4001.
 [http://dx.doi.org/10.3892/ol.2017.6017] [PMID: 28599405]

[69]
Smadbeck, J.; Peterson, M.B.; Zee, B.M.; Garapaty, S.; Mago, A.; Lee, C.; Giannis, A.; Trojer, P.; Garcia, B.A.; Floudas, C.A. De novo peptide design and experimental validation of histone methyltransferase inhibitors. PLoS One,  2014, 9(2), e90095.
 [http://dx.doi.org/10.1371/journal.pone.0090095] [PMID: 24587223]

[70]
Trivedi, M.; Zhang, Y.; Toledano, L.M.; Clarke, A.; Deth, R. Differential neurogenic effects of casein-derived opioid peptides on neuronal stem cells: Implications for redox-based epigenetic changes. J. Nutr. Biochem.,  2016, 37, 39-46.
 [http://dx.doi.org/10.1016/j.jnutbio.2015.10.012] [PMID: 27611101]

[71]
Li, Y.; Jin, T.; Liu, N.; Wang, J.; Qin, Z.; Yin, S.; Zhang, Y.; Fu, Z.; Wu, Y.; Wang, Y.; Liu, Y.; Yang, M.; Pang, A.; Sun, J.; Wang, Y.; Yang, X. A short peptide exerts neuroprotective effects on cerebral ischemia–reperfusion injury by reducing inflammation via the miR-6328/IKKβ/NF-κB axis. J. Neuroinflammation,  2023, 20(1), 53.
 [http://dx.doi.org/10.1186/s12974-023-02739-4] [PMID: 36855153]

[72]
Li, S.; Lei, Z.; Sun, T. The role of microRNAs in neurodegenerative diseases: A review. Cell Biol. Toxicol.,  2023, 39(1), 53-83.
 [http://dx.doi.org/10.1007/s10565-022-09761-x] [PMID: 36125599]

[73]
Linnerbauer, M.; Wheeler, M.A.; Quintana, F.J. Astrocyte crosstalk in CNS inflammation. Neuron,  2020, 108(4), 608-622.
 [http://dx.doi.org/10.1016/j.neuron.2020.08.012] [PMID: 32898475]

[74]
Ano, Y.; Yoshino, Y.; Kutsukake, T.; Ohya, R.; Fukuda, T.; Uchida, K.; Takashima, A.; Nakayama, H. Tryptophan-related dipeptides in fermented dairy products suppress microglial activation and prevent cognitive decline. Aging,  2019, 11(10), 2949-2967.
 [http://dx.doi.org/10.18632/aging.101909] [PMID: 31121563]

[75]
Muzio, L.; Viotti, A.; Martino, G. Microglia in neuroinflammation and neurodegeneration: from understanding to therapy. Front. Neurosci.,  2021, 15, 742065.
 [http://dx.doi.org/10.3389/fnins.2021.742065] [PMID: 34630027]

[76]
Liddelow, S.A.; Guttenplan, K.A.; Clarke, L.E.; Bennett, F.C.; Bohlen, C.J.; Schirmer, L.; Bennett, M.L.; Münch, A.E.; Chung, W.S.; Peterson, T.C.; Wilton, D.K.; Frouin, A.; Napier, B.A.; Panicker, N.; Kumar, M.; Buckwalter, M.S.; Rowitch, D.H.; Dawson, V.L.; Dawson, T.M.; Stevens, B.; Barres, B.A. Neurotoxic reactive astrocytes are induced by activated microglia. Nature,  2017, 541(7638), 481-487.
 [http://dx.doi.org/10.1038/nature21029] [PMID: 28099414]

[77]
García, F.S.; Balsells, S.A.; Longueville, S.; Hervé, D.; Gruart, A.; García, D.J.M.; Alberch, J.; Giralt, A. Astrocytic BDNF and TrkB regulate severity and neuronal activity in mouse models of temporal lobe epilepsy. Cell Death Dis.,  2020, 11(6), 411.
 [http://dx.doi.org/10.1038/s41419-020-2615-9] [PMID: 32483154]

[78]
Zhang, Q.; Su, G.; Zhao, T.; Sun, B.; Zheng, L.; Zhao, M. Neuroprotection of round scad (Decapterus maruadsi) hydrolysate in glutamate-damaged PC12 cells: Possible involved signaling pathways and potential bioactive peptides. J. Funct. Foods,  2020, 64, 103690.
 [http://dx.doi.org/10.1016/j.jff.2019.103690]

[79]
Liu, C.; Guo, Y.; Zhao, F.; Qin, H.; Lu, H.; Fang, L.; Wang, J.; Min, W. Potential mechanisms mediating the protective effects of a peptide from walnut ( Juglans mandshurica Maxim.) against hydrogen peroxide induced neurotoxicity in PC12 cells. Food Funct.,  2019, 10(6), 3491-3501.
 [http://dx.doi.org/10.1039/C8FO02557F] [PMID: 31143910]

[80]
Zuccato, C.; Cattaneo, E. Brain-derived neurotrophic factor in neurodegenerative diseases. Nat. Rev. Neurol.,  2009, 5(6), 311-322.
 [http://dx.doi.org/10.1038/nrneurol.2009.54] [PMID: 19498435]

[81]
Lim, J.L.; Wilhelmus, M.M.M.; de Vries, H.E.; Drukarch, B.; Hoozemans, J.J.M.; van Horssen, J. Antioxidative defense mechanisms controlled by Nrf2: State-of-the-art and clinical perspectives in neurodegenerative diseases. Arch. Toxicol.,  2014, 88(10), 1773-1786.
 [http://dx.doi.org/10.1007/s00204-014-1338-z] [PMID: 25164826]

[82]
Shimizu, A.; Mitani, T.; Tanaka, S.; Fujii, H.; Maebuchi, M.; Amiya, Y.; Tanaka, M.; Matsui, T.; Nakamura, S.; Katayama, S. Soybean-derived glycine–arginine dipeptide administration promotes neurotrophic factor expression in the mouse brain. J. Agric. Food Chem.,  2018, 66(30), 7935-7941.
 [http://dx.doi.org/10.1021/acs.jafc.8b01581] [PMID: 29985005]

[83]
Liu, H.J.; Yan, J. Crop genome-wide association study: A harvest of biological relevance. Plant J.,  2019, 97(1), 8-18.
 [http://dx.doi.org/10.1111/tpj.14139] [PMID: 30368955]

[84]
Jin, M.M.; Zhang, L.; Yu, H.X.; Meng, J.; Sun, Z.; Lu, R.R. Protective effect of whey protein hydrolysates on H2O2-induced PC12 cells oxidative stress via a mitochondria-mediated pathway. Food Chem.,  2013, 141(2), 847-852.
 [http://dx.doi.org/10.1016/j.foodchem.2013.03.076] [PMID: 23790857]

[85]
Tata, A.M.; Velluto, L.; D’Angelo, C.; Reale, M. Cholinergic system dysfunction and neurodegenerative diseases: cause or effect? Disord.,  2014, 13(7), 1294-1303.
 [PMID: 25230223]

[86]
Zhang, Q.X.; Jin, M.M.; Zhang, L.; Yu, H.X.; Sun, Z.; Lu, R.R. Hydrophobicity of whey protein hydrolysates enhances the protective effect against oxidative damage on PC 12 cells. J. Dairy Res.,  2015, 82(1), 1-7.
 [http://dx.doi.org/10.1017/S0022029914000405] [PMID: 25287524]

[87]
Hou, R.C.W.; Chen, Y.S.; Huang, J.R.; Jeng, K.C.G. Cross-linked bromelain inhibits lipopolysaccharide-induced cytokine production involving cellular signaling suppression in rats. J. Agric. Food Chem.,  2006, 54(6), 2193-2198.
 [http://dx.doi.org/10.1021/jf052390k] [PMID: 16536595]

[88]
Jeong, H.K.; Ji, K.; Min, K.; Joe, E.H. Brain inflammation and microglia: Facts and misconceptions. Exp. Neurobiol.,  2013, 22(2), 59-67.
 [http://dx.doi.org/10.5607/en.2013.22.2.59] [PMID: 23833554]

[89]
Chai, H.J.; Wu, C.J.; Yang, S.H.; Li, T.L.; Sun Pan, B. Peptides from hydrolysate of lantern fish (Benthosema pterotum) proved neuroprotective in vitro and in vivo. J. Funct. Foods,  2016, 24, 438-449.
 [http://dx.doi.org/10.1016/j.jff.2016.04.009]

[90]
Liao, X.; Zhu, Z.; Wu, S.; Chen, M.; Huang, R.; Wang, J.; Wu, Q.; Ding, Y. Preparation of antioxidant protein hydrolysates from Pleurotus geesteranus and their protective effects on H2O2 oxidative damaged PC12 cells. Molecules,  2020, 25(22), 5408.
 [http://dx.doi.org/10.3390/molecules25225408] [PMID: 33227951]

[91]
Zhao, Y.; Lu, Z.; Xu, X.; Sun, N.; Lin, S. Sea cucumber-derived peptide attenuates scopolamine-induced cognitive impairment by preventing hippocampal cholinergic dysfunction and neuronal cell death. J. Agric. Food Chem.,  2022, 70(2), 567-576.
 [http://dx.doi.org/10.1021/acs.jafc.1c07232] [PMID: 34989228]

[92]
Zhao, T.; Su, G.; Wang, S.; Zhang, Q.; Zhang, J.; Zheng, L.; Sun, B.; Zhao, M. Neuroprotective effects of acetylcholinesterase inhibitory peptides from anchovy ( Coilia mystus ) against glutamate-induced toxicity in PC12 cells. J. Agric. Food Chem.,  2017, 65(51), 11192-11201.
 [http://dx.doi.org/10.1021/acs.jafc.7b03945] [PMID: 29190426]

[93]
Lee, S.Y.; Hur, S.J. Protective effect of a 3 kDa peptide obtained from beef myofibrillar protein using alkaline-AK on neuronal cells. Neurochem. Int.,  2019, 129, 104459.
 [http://dx.doi.org/10.1016/j.neuint.2019.05.003] [PMID: 31077759]

[94]
Lee, S.Y.; Hur, S.J. Neuroprotective effects of different molecular weight peptide fractions obtained from beef by hydrolysis with commercial enzymes in SH-SY5Y cells. Food Res. Int.,  2019, 121, 176-184.
 [http://dx.doi.org/10.1016/j.foodres.2019.03.039] [PMID: 31108738]

[95]
Xin, J.L.; Zhang, Y.; Li, Y.; Zhang, L.Z.; Lin, Y.; Zheng, L.W. Protective effects of cervus nippon temminck velvet antler polypeptides against MPP+-induced cytotoxicity in SH-SY5Y neuroblastoma cells. Mol. Med. Rep.,  2017, 16(4), 5143-5150.
 [http://dx.doi.org/10.3892/mmr.2017.7303] [PMID: 28849030]

[96]
Wu, D.; Li, M.; Ding, J.; Zheng, J.; Zhu, B.; Lin, S. Structure-activity relationship and pathway of antioxidant shrimp peptides in a PC12 cell model. J. Funct. Foods,  2020, 70, 103978.
 [http://dx.doi.org/10.1016/j.jff.2020.103978]

[97]
Vo, T.S.; Ngo, D.H.; Kim, J.A.; Ryu, B.; Kim, S.K. An antihypertensive peptide from tilapia gelatin diminishes free radical formation in murine microglial cells. J. Agric. Food Chem.,  2011, 59(22), 12193-12197.
 [http://dx.doi.org/10.1021/jf202837g] [PMID: 22004328]

[98]
Barbosa, E.A.; Oliveira, A.; Plácido, A.; Socodato, R.; Portugal, C.C.; Mafud, A.C.; Ombredane, A.S.; Moreira, D.C.; Vale, N.; Bessa, L.J.; Joanitti, G.A.; Alves, C.; Gomes, P.; Delerue-Matos, C.; Mascarenhas, Y.P.; Marani, M.M.; Relvas, J.B.; Pintado, M.; Leite, J.R.S.A. Structure and function of a novel antioxidant peptide from the skin of tropical frogs. Free Radic. Biol. Med.,  2018, 115, 68-79.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2017.11.001] [PMID: 29162516]

[99]
Feng, L.; Wang, X.; Peng, F.; Liao, J.; Nai, Y.; Lei, H.; Li, M.; Xu, H. Walnut protein hydrolysates play a protective role on neurotoxicity induced by d-galactose and aluminum chloride in mice. Molecules,  2018, 23(9), 2308.
 [http://dx.doi.org/10.3390/molecules23092308] [PMID: 30201912]

[100]
Zou, J.; Cai, P.; Xiong, C.; Ruan, J. Neuroprotective effect of peptides extracted from walnut (Juglans Sigilata Dode) proteins on Aβ25-35-induced memory impairment in mice. J. Huazhong Univ. Sci. Technolog. Med. Sci.,  2016, 36(1), 21-30.
 [http://dx.doi.org/10.1007/s11596-016-1536-4] [PMID: 26838735]

[101]
Wang, S.; Zheng, L.; Zhao, T.; Zhang, Q.; Liu, Y.; Sun, B.; Su, G.; Zhao, M. Inhibitory effects of walnut ( Juglans regia ) peptides on neuroinflammation and oxidative stress in lipopolysaccharide-induced cognitive impairment mice. J. Agric. Food Chem.,  2020, 68(8), 2381-2392.
 [http://dx.doi.org/10.1021/acs.jafc.9b07670] [PMID: 32037817]

[102]
Wattanathorn, J.; Thukham-mee, W.; Muchimapura, S.; Wannanon, P.; Tong-un, T.; Tiamkao, S. Preventive effect of cashew-derived protein hydrolysate with high fiber on cerebral ischemia. BioMed Res. Int.,  2017, 2017, 6135023.
 [http://dx.doi.org/10.1155/2017/6135023]

[103]
Jin, W.; Xu, X.; Chen, X.; Qi, W.; Lu, J.; Yan, X.; Zhao, D.; Cong, D.; Li, X.; Sun, L. Protective effect of pig brain polypeptides against corticosterone-induced oxidative stress, inflammatory response, and apoptosis in PC12 cells. Biomed. Pharmacother.,  2019, 115, 108890.
 [http://dx.doi.org/10.1016/j.biopha.2019.108890] [PMID: 31022597]

[104]
Chataigner, M.; Mortessagne, P.; Lucas, C.; Pallet, V.; Layé, S.; Mehaignerie, A.; Bouvret, E.; Dinel, A.L.; Joffre, C. Dietary fish hydrolysate supplementation containing n-3 LC-PUFAs and peptides prevents short-term memory and stress response deficits in aged mice. Brain Behav. Immun.,  2021, 91, 716-730.
 [http://dx.doi.org/10.1016/j.bbi.2020.09.022] [PMID: 32976934]

[105]
Morris, J.L.; Gillet, G.; Prudent, J.; Popgeorgiev, N. Bcl-2 family of proteins in the control of mitochondrial calcium signalling: An old chap with new roles. Int. J. Mol. Sci.,  2021, 22(7), 3730.
 [http://dx.doi.org/10.3390/ijms22073730] [PMID: 33918511]

[106]
Zhang, Z.; Ge, X.; Luo, X.; Wang, P.; Fan, Q.; Hu, G.; Xiao, J.; Li, F.; Wu, J. Simultaneous editing of two copies of Gh14-3-3d confers enhanced transgene-clean plant defense against Verticillium dahliae in allotetraploid upland cotton. Front. Plant Sci.,  2018, 9, 842.
 [http://dx.doi.org/10.3389/fpls.2018.00842] [PMID: 30013582]

[107]
Yang, J.; Fang, L.; Lu, H.; Liu, C.; Wang, J.; Wu, D.; Min, W. Walnut-derived peptide enhances mitophagy via JNK-mediated PINK1 activation to reduce oxidative stress in HT-22 cells. J. Agric. Food Chem.,  2022, 70(8), 2630-2642.
 [http://dx.doi.org/10.1021/acs.jafc.2c00005] [PMID: 35187930]
Cite As
Current Topics in Medicinal Chemistry

Food-derived Peptides as Promising Neuroprotective Agents: Mechanism and Therapeutic Potential

Abstract

Graphical Abstract
