β-Lactolin improves mitochondrial function in Aβ-treated mouse hippocampal neuronal cell line and a human iPSC-derived neuronal cell model of Alzheimer's disease.
Alzheimer's disease
amyloid β
mitochondria
neuronal cell
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
06
03
2022
received:
27
08
2021
accepted:
14
03
2022
entrez:
23
3
2022
pubmed:
24
3
2022
medline:
23
4
2022
Statut:
ppublish
Résumé
Mitochondrial dysfunctions are a key hallmark of Alzheimer's disease (AD). β-Lactolin, a whey-derived glycine-threonine-tryptophan-tyrosine tetrapeptide, has been previously reported to prevent AD-like pathologies in an AD mouse model via regulation of microglial functions. However, the direct effect of β-lactolin on neuronal cells and neuronal mitochondrial functions remains unknown. Here, we investigated the effects of β-lactolin on mitochondrial functions in amyloid β (Aβ)-treated mouse hippocampal neuronal HT22 cells and human induced-pluripotent cell (hiPSC)-derived AD model neurons. Adding β-lactolin to Aβ-treated HT22 cells increased both the oxygen consumption rate and cellular ATP concentrations, suggesting that β-lactolin improves mitochondrial respiration and energy production. Using high content image analysis, we found that β-lactolin improved mitochondrial fragmentation, membrane potential, and oxidative stress in Aβ-treated cells, eventually preventing neuronal cell death. From a mechanistic perspective, we found that β-lactolin increased gene expression of mitofusin-2, which contributes to mitochondrial fusion events. Finally, we showed that β-lactolin improves both mitochondrial morphologies and membrane potentials in hiPSC-derived AD model neurons. Taken together, β-lactolin improved mitochondrial functions AD-related neuronal cell models and prevented neuronal cell death. The dual function of β-lactolin on both neuron and microglia marks an advantage in maintaining neuronal health.
Identifiants
pubmed: 35319792
doi: 10.1096/fj.202101366RR
doi:
Substances chimiques
Amyloid beta-Peptides
0
Oligopeptides
0
Whey Proteins
0
beta-lactolin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22277Informations de copyright
© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
Références
Glenner GG, Wong CW. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Comm. 1984;120:885-890.
Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med. 2010;362:329-344.
Amor S, Puentes F, Baker D, van der Valk P. Inflammation in neurodegenerative diseases. Immunology. 2010;129:154-169.
Fung A, Vizcaychipi M, Lloyd D, Wan Y, Ma D. Central nervous system inflammation in disease related conditions: mechanistic prospects. Brain Res. 2012;1446:144-155.
Cadonic C, Sabbir MG, Albensi BC. Mechanisms of mitochondrial dysfunction in Alzheimer's disease. Mol Neurobiol. 2016;53:6078-6090.
Cha M-Y, Han S-H, Son SM, et al. Mitochondria-specific accumulation of amyloid β induces mitochondrial dysfunction leading to apoptotic cell death. PLoS One. 2012;7:e34929.
Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. Cell. 2012;148:1145-1159.
Hoppins S, Lackner L, Nunnari J. The machines that divide and fuse mitochondria. Annu Rev Biochem. 2007;76:751-780.
Archer SL. Mitochondrial dynamics-mitochondrial fission and fusion in human diseases. N Engl J Med. 2013;369:2236-2251.
Bertholet AM, Delerue T, Millet AM, et al. Mitochondrial fusion/fission dynamics in neurodegeneration and neuronal plasticity. Neurobiol Dis. 2016;90:3-19.
Martinou J-C, Youle RJ. Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell. 2011;21:92-101.
Fukuyama H, Ogawa M, Yamauchi H, et al. Altered cerebral energy metabolism in Alzheimer's disease: a PET study. J Nucl Med. 1994;35:1-6.
Chandrasekaran K, Hatanpää K, Brady DR, Rapoport SI. Evidence for physiological down-regulation of brain oxidative phosphorylation in Alzheimer's disease. Exp Neurol. 1996;142:80-88.
Caspersen C, Wang N, Yao J, et al. Mitochondrial Aβ: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease. FASEB J. 2005;19:2040-2041.
Hauptmann S, Scherping I, Dröse S, et al. Mitochondrial dysfunction: an early event in Alzheimer pathology accumulates with age in AD transgenic mice. Neurobiol Aging. 2009;30:1574-1586.
Fu Y-J, Xiong S, Lovell MA, Lynn BC. Quantitative proteomic analysis of mitochondria in aging PS-1 transgenic mice. Cell Mol Neurobiol. 2009;29:649-664.
Wu Z, Zhu Y, Cao X, Sun S, Zhao B. Mitochondrial toxic effects of Aβ through mitofusins in the early pathogenesis of Alzheimer's disease. Mol Neurobiol. 2014;50:986-996.
Kang S, Byun J, Son SM, Mook-Jung I. Thrombospondin-1 protects against Aβ-induced mitochondrial fragmentation and dysfunction in hippocampal cells. Cell Death Discov. 2018;4:1-12.
Wang X, Su B, Lee H-G, et al. Impaired balance of mitochondrial fission and fusion in Alzheimer's disease. J Neurosci. 2009;29:9090-9103.
Reddy PH, Yin X, Manczak M, et al. Mutant APP and amyloid beta-induced defective autophagy, mitophagy, mitochondrial structural and functional changes and synaptic damage in hippocampal neurons from Alzheimer's disease. Hum Mol Genet. 2018;27:2502-2516.
Wang X, Su B, Zheng L, Perry G, Smith MA, Zhu X. The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer's disease. J Neurochem. 2009;109:153-159.
Perez Ortiz JM, Swerdlow RH. Mitochondrial dysfunction in Alzheimer's disease: role in pathogenesis and novel therapeutic opportunities. Br J Pharmacol. 2019;176:3489-3507.
Camfield DA, Owen L, Scholey AB, Pipingas A, Stough C. Dairy constituents and neurocognitive health in ageing. Br J Nutr. 2011;106:159-174.
Ozawa M, Ninomiya T, Ohara T, et al. Dietary patterns and risk of dementia in an elderly Japanese population: the Hisayama Study. Am J Clin Nutr. 2013;97:1076-1082.
Ano Y, Ozawa M, Kutsukake T, et al. Preventive effects of a fermented dairy product against Alzheimer's disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity. PLoS One. 2015;10:e0118512.
Ano Y, Ayabe T, Kutsukake T, et al. Novel lactopeptides in fermented dairy products improve memory function and cognitive decline. Neurobiol Aging. 2018;72:23-31.
Ano Y, Ohya R, Takaichi Y, et al. β-lactolin, a whey-derived lacto-tetrapeptide, prevents Alzheimer's disease pathologies and cognitive decline. J Alzheimers Dis. 2020;73:1331-1342.
Park YH, Shin SJ, Kim HS, et al. Omega-3 fatty acid-type docosahexaenoic acid protects against Aβ-mediated mitochondrial deficits and pathomechanisms in Alzheimer's disease-related animal model. Int J Mol Sci. 2020;21:3879.
Honda M, Minami I, Tooi N, et al. The modeling of Alzheimer's disease by the overexpression of mutant Presenilin 1 in human embryonic stem cells. Biochem Biophys Res Comm. 2016;469:587-592.
Connolly NM, Düssmann H, Anilkumar U, Huber HJ, Prehn JH. Single-cell imaging of bioenergetic responses to neuronal excitotoxicity and oxygen and glucose deprivation. J Neurosci. 2014;34:10192-10205.
Brand MD, Nicholls DG. Assessing mitochondrial dysfunction in cells. Biochem J. 2011;435:297-312.
Dranka BP, Benavides GA, Diers AR, et al. Assessing bioenergetic function in response to oxidative stress by metabolic profiling. Free Radic Biol Med. 2011;51:1621-1635.
Connolly NMC, Theurey P, Adam-Vizi V, et al. Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases. Cell Death Differ. 2018;25:542-572.
Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol. 2003;160:189-200.
Park J, Choi H, Min JS, et al. Loss of mitofusin 2 links beta-amyloid-mediated mitochondrial fragmentation and Cdk5-induced oxidative stress in neuron cells. J Neurochem. 2015;132:687-702.
Reddy PH, Manczak M, Yin X, et al. Protective effects of a natural product, curcumin, against amyloid β induced mitochondrial and synaptic toxicities in Alzheimer's disease. J Investig Med. 2016;64:1220-1234.
Reddy PH, Manczak M, Yin X. Mitochondria-division inhibitor 1 protects against amyloid-β induced mitochondrial fragmentation and synaptic damage in Alzheimer's disease. J Alzheimers Dis. 2017;58:147-162.
Ayabe T, Ano Y, Ohya R, Kitaoka S, Furuyashiki T. The lacto-tetrapeptide Gly-Thr-Trp-Tyr, β-Lactolin, improves spatial memory functions via dopamine release and D1 receptor activation in the hippocampus. Nutrients. 2019;11:2469.
Ayabe T, Ohya R, Ano Y. β-lactolin, a whey-derived glycine-threonine-tryptophan-tyrosine lactotetrapeptide, improves prefrontal cortex-associated reversal learning in mice. Biosci Biotechnol Biochem. 2020;84:1039-1046.
Ramsay RR. Molecular aspects of monoamine oxidase B. Prog Neuropsychopharmacol Biol Psychiatry. 2016;69:81-89.
Mishra A, Singh S, Tiwari V, Chaturvedi S, Wahajuddin M, Shukla S. Dopamine receptor activation mitigates mitochondrial dysfunction and oxidative stress to enhance dopaminergic neurogenesis in 6-OHDA lesioned rats: a role of Wnt signalling. Neurochem Int. 2019;129:104463.
Mishra A, Singh S, Tiwari V, Bano S, Shukla S. Dopamine D1 receptor agonism induces dynamin related protein-1 inhibition to improve mitochondrial biogenesis and dopaminergic neurogenesis in rat model of Parkinson's disease. Behav Brain Res. 2020;378:112304.
Du H, Guo L, Yan S, Sosunov AA, McKhann GM, Yan SS. Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model. Proc Natl Acad Sci. 2010;107:18670-18675.
Calkins MJ, Manczak M, Mao P, Shirendeb U, Reddy PH. Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer's disease. Hum Mol Genet. 2011;20:4515-4529.
Dixit S, Fessel JP, Harrison FE. Mitochondrial dysfunction in the APP/PSEN1 mouse model of Alzheimer's disease and a novel protective role for ascorbate. Free Radic Biol Med. 2017;112:515-523.
Shin SJ, Jeon SG, Kim J-I, et al. Red ginseng attenuates Aβ-induced mitochondrial dysfunction and Aβ-mediated pathology in an animal model of Alzheimer's disease. Int J Mol Sci. 2019;20:3030.
Ano Y, Ohya R, Kondo K. Antidepressant-like effect of β-lactolin, a glycine-threonine-tryptophan-tyrosine peptide. J Nutr Sci Vitaminol. 2019;65:430-434.
Cerejeira J, Lagarto L, Mukaetova-Ladinska E. Behavioral and psychological symptoms of dementia. Front Neurol. 2012;3:73.
Manji H, Kato T, Di Prospero NA, et al. Impaired mitochondrial function in psychiatric disorders. Nat Rev Neurosci. 2012;13:293-307.
Wisniewski T, Dowjat WK, Buxbaum JD, et al. A novel Polish presenilin-1 mutation (P117L) is associated with familial Alzheimer's disease and leads to death as early as the age of 28 years. NeuroReport. 1998;9:217-221.
Kuperstein I, Broersen K, Benilova I, et al. Neurotoxicity of Alzheimer's disease Aβ peptides is induced by small changes in the Aβ42 to Aβ40 ratio. EMBO J. 2010;29:3408-3420.
Pauwels K, Williams TL, Morris KL, et al. Structural basis for increased toxicity of pathological aβ42: aβ40 ratios in Alzheimer disease. J Biol Chem. 2012;287:5650-5660.
Kita M, Obara K, Kondo S, Umeda S, Ano Y. Effect of supplementation of a whey peptide rich in tryptophan-tyrosine-related peptides on cognitive performance in healthy adults: a randomized, double-blind, placebo-controlled study. Nutrients. 2018;10:899.
Kita M, Kobayashi K, Obara K, Koikeda T, Umeda S, Ano Y. Supplementation with whey peptide rich in β-lactolin improves cognitive performance in healthy older adults: a randomized, double-blind, placebo-controlled study. Front Neurosci. 2019;13:399.
Terada T, Obi T, Bunai T, et al. In vivo mitochondrial and glycolytic impairments in patients with Alzheimer disease. Neurology. 2020;94:e1592-e1604.
Mansur A, Rabiner EA, Tsukada H, et al. Test-retest variability and reference region-based quantification of 18F-BCPP-EF for imaging mitochondrial complex I in the human brain. J Cereb Blood Flow Metab. 2021;41(4):771-779.
Ano Y, Kita M, Kobayashi K, Koikeda T, Kawashima R. Effects of β-lactolin on regional cerebral blood flow within the dorsolateral prefrontal cortex during working memory task in healthy adults: a randomized controlled trial. J Clin Med. 2021;10:480.
Ano Y, Kobayashi K, Hanyuda M, Kawashima R. β-lactolin increases cerebral blood flow in dorsolateral prefrontal cortex in healthy adults: a randomized controlled trial. Aging. 2020;12:18660.
Ano Y, Kobayashi K, Koikeda T, Kawashima R. β-lactolin, a whey-derived Gly-Thr-Trp-Tyr lactopeptide, promotes cerebral blood flow during cognitive tasks: a randomized controlled trial. Curr Dev Nutr. 2021;5:889.
Fabiani M, Gordon BA, Maclin EL, et al. Neurovascular coupling in normal aging: a combined optical, ERP and fMRI study. NeuroImage. 2014;85:592-607.
Tarantini S, Tran CHT, Gordon GR, Ungvari Z, Csiszar A. Impaired neurovascular coupling in aging and Alzheimer's disease: contribution of astrocyte dysfunction and endothelial impairment to cognitive decline. Exp Gerontol. 2017;94:52-58.
Jack C, Del Olmo A, Valles S. Can mild cognitive impairment be stabilized by showering brain mitochondria with laser photons? Neuropharmacology. 2020;171:107841.
Tarantini S, Valcarcel-Ares NM, Yabluchanskiy A, et al. Treatment with the mitochondrial-targeted antioxidant peptide SS-31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice. Aging Cell. 2018;17:e12731.