Characterisation of the Mouse Cerebellar Proteome in the GFAP-IL6 Model of Chronic Neuroinflammation.
Bioinformatics
Chronic inflammation
Metabolic dysregulation
Motor function
Neurodegeneration
Protein aggregation
Top-down proteomics
Journal
Cerebellum (London, England)
ISSN: 1473-4230
Titre abrégé: Cerebellum
Pays: United States
ID NLM: 101089443
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
accepted:
25
06
2021
pubmed:
30
7
2021
medline:
18
5
2022
entrez:
29
7
2021
Statut:
ppublish
Résumé
GFAP-IL6 transgenic mice are characterised by astroglial and microglial activation predominantly in the cerebellum, hallmarks of many neuroinflammatory conditions. However, information available regarding the proteome profile associated with IL-6 overexpression in the mouse brain is limited. This study investigated the cerebellum proteome using a top-down proteomics approach using 2-dimensional gel electrophoresis followed by liquid chromatography-coupled tandem mass spectrometry and correlated these data with motor deficits using the elevated beam walking and accelerod tests. In a detailed proteomic analysis, a total of 67 differentially expressed proteoforms including 47 cytosolic and 20 membrane-bound proteoforms were identified. Bioinformatics and literature mining analyses revealed that these proteins were associated with three distinct classes: metabolic and neurodegenerative processes as well as protein aggregation. The GFAP-IL6 mice exhibited impaired motor skills in the elevated beam walking test measured by their average scores of 'number of footslips' and 'time to traverse' values. Correlation of the proteoforms' expression levels with the motor test scores showed a significant positive correlation to peroxiredoxin-6 and negative correlation to alpha-internexin and mitochondrial cristae subunit Mic19. These findings suggest that the observed changes in the proteoform levels caused by IL-6 overexpression might contribute to the motor function deficits.
Identifiants
pubmed: 34324160
doi: 10.1007/s12311-021-01303-1
pii: 10.1007/s12311-021-01303-1
doi:
Substances chimiques
Interleukin-6
0
Proteome
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
404-424Subventions
Organisme : University of Western Sydney
ID : APP1121813
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Gyengesi E, Rangel A, Ullah F, Liang H, Niedermayer G, Asgarov R, Venigalla M, Gunawardena D, Karl T, Munch G. Chronic microglial activation in the GFAP-IL6 mouse contributes to age-dependent cerebellar volume loss and impairment in motor function. Front Neurosci. 2019;13:303.
pubmed: 31001075
pmcid: 6456818
Walker KA. Inflammation and neurodegeneration: chronicity matters. Aging. 2018;11(1):3–4.
pubmed: 30554190
pmcid: 6339781
Chitnis T, Weiner HL. CNS inflammation and neurodegeneration. J Clin Invest. 2017;127(10):3577–87.
pubmed: 28872464
pmcid: 5617655
Gyengési E, Muench G. In search of an anti-inflammatory drug for Alzheimer disease. Nat Rev Neurol. 2020;16(3):131–2.
pubmed: 31919414
DiSabato DJ, Quan N, Godbout JP. Neuroinflammation: the devil is in the details. J Neurochem. 2016;139:136–53.
pubmed: 26990767
pmcid: 5025335
Morales I, Guzmán-Martínez L, Cerda-Troncoso C, Farías GA, Maccioni RB. Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches. Front Cell Neurosci 2014;8:(112).
Godbout JP, Johnson RW. Interleukin-6 in the aging brain. J Neuroimmunol. 2004;147(1):141–4.
pubmed: 14741447
Huell M, Strauss S, Volk B, Berger M, Bauer J. Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer’s disease patients. Acta Neuropathol. 1995;89(6):544–51.
pubmed: 7676810
Hüll M, Fiebich BL, Lieb K, Strauss S, Berger M, Volk B, Bauer J. Interleukin-6-associated inflammatory processes in Alzheimer’s disease: new therapeutic options. Neurobiol Aging. 1996;17(5):795–800.
pubmed: 8892354
Bettcher BM, Watson CL, Walsh CM, Lobach IV, Neuhaus J, Miller JW, Green R, Patel N, Dutt S, Busovaca E, et al. Interleukin-6, age, and corpus callosum integrity. PLoS One 2014;9(9):e106521.
Singh-Manoux A, Dugravot A, Brunner E, Kumari M, Shipley M, Elbaz A, Kivimaki M. Interleukin-6 and C-reactive protein as predictors of cognitive decline in late midlife. Neurol. 2014;83(6):486–93.
Quintanilla RA, Orellana DI, González-Billault C, Maccioni RB. Interleukin-6 induces Alzheimer-type phosphorylation of tau protein by deregulating the cdk5/p35 pathway. Exp Cell Res. 2004;295(1):245–57.
pubmed: 15051507
Gruol DL, Nelson TE. Purkinje neuron physiology is altered by the inflammatory factor interleukin-6. Cerebellum. 2005;4(3):198–205.
pubmed: 16147952
Campbell IL, Abraham CR, Masliah E, Kemper P, Inglis JD, Oldstone MB, Mucke L. Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci. 1993;90(21):10061–5.
pubmed: 7694279
pmcid: 47713
Chiang CS, Stalder A, Samimi A, Campbell IL. Reactive gliosis as a consequence of interleukin-6 expression in the brain: studies in transgenic mice. Develop Neurosci. 1994;16(3–4):212–21.
Ullah F, Asgarov R, Venigalla M, Liang H, Niedermayer G, Münch G, Gyengesi E. Effects of a solid lipid curcumin particle formulation on chronic activation of microglia and astroglia in the GFAP-IL6 mouse model. Sci Rep. 2020;10(1):2365.
pubmed: 32047191
pmcid: 7012877
Castelnau PA, Garrett RS, Palinski W, Witztum JL, Campbell IL, Powell HC. Abnormal iron deposition associated with lipid peroxidation in transgenic mice expressing interleukin-6 in the brain. J Neuropathol Exp Neurol. 1998;57(3):268–82.
pubmed: 9600219
Heyser CJ, Masliah E, Samimi A, Campbell IL, Gold LH. Progressive decline in avoidance learning paralleled by inflammatory neurodegeneration in transgenic mice expressing interleukin 6 in the brain. Proc Natl Acad Sci. 1997;94(4):1500–5.
pubmed: 9037082
pmcid: 19820
Coorssen JR, Yergey AL. Proteomics is analytical chemistry: fitness-for-purpose in the application of top-down and bottom-up analyses. Proteome. 2015;3(4):440–53.
Shevchenko G, Konzer A, Musunuri S, Bergquist J. Neuroproteomics tools in clinical practice. BBA. 2015;1854(7):705–17.
pubmed: 25680928
Hanash S. Disease proteomics. Nat. 2003;422(6928):226–32.
Fasano M, Monti C, Alberio T. A systems biology-led insight into the role of the proteome in neurodegenerative diseases. Expert Rev Proteomics. 2016;13(9):845–55.
pubmed: 27477319
Davidsson P, Sjögren M. The use of proteomics in biomarker discovery in neurodegenerative diseases. Dis Markers. 2005;21(2):81–92.
pubmed: 15920295
pmcid: 3850612
Anderson NL, Anderson NG. Proteome and proteomics: new technologies, new concepts, and new words. Electrophoresis. 1998;19(11):1853–61.
pubmed: 9740045
Sen MK, Almuslehi MSM, Gyengesi E, Myers SJ, Shortland PJ, Mahns DA, Coorssen JR. Suppression of the peripheral immune system limits the central immune response following cuprizone-feeding: relevance to modelling multiple sclerosis. Cells. 2019;8(11):1314.
pmcid: 6912385
Butterfield DA. Proteomics: a new approach to investigate oxidative stress in Alzheimer’s disease brain. Brain Res. 2004;1000(1):1–7.
pubmed: 15053946
Wright EP, Partridge MA, Padula MP, Gauci VJ, Malladi CS, Coorssen JR. Top-down proteomics: enhancing 2D gel electrophoresis from tissue processing to high-sensitivity protein detection. Proteomics. 2014;14(7–8):872–89.
pubmed: 24452924
Görg A, Boguth G, Obermaier C, Posch A, Weiss W. Two-dimensional polyacrylamide gel electrophoresis with immobilized pH gradients in the first dimensin (IPG-Dalt): the state of the art and the controversy of vertical versus horizontal systems. Electrophoresis. 1995;16(1):1079–86.
pubmed: 7498150
Gorg A, Weiss W, Dunn MJ. Current two-dimensional electrophoresis technology for proteomics. Proteomics. 2004;4(12):3665–85.
pubmed: 15543535
Görg A, Postel W, Günther S. Two-dimensional electrophoresis. The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 1988;9(9):531–546.
Gorg A, Drews O, Luck C, Weiland F, Weiss W. 2-DE with IPGs. Electrophoresis. 2009;30:122–32.
Bjellqvist B, Ek K, Righetti PG, Gianazza E, Gorg A, Westermeier R, Postel W. Isoelectric focusing in immobilized pH gradients: principle, methodology and some applications. J Biochem Biophys Methods. 1982;6(4):317–39.
pubmed: 7142660
Diedrich M, Kitada T, Nebrich G, Koppelstaetter A, Shen J, Zabel C, Klose J, Mao L. Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson’s disease. Proteome Sci. 2011;9:59–59.
pubmed: 21943346
pmcid: 3196908
Burgula S, Medisetty R, Jammulamadaka N, Musturi S, Ilavazhagan G, Singh SS. Downregulation of PEBP1 in rat brain cortex in hypoxia. J Mol Neurosci. 2010;41(1):36–47.
pubmed: 19705086
Joerchel S, Raap M, Bigl M, Eschrich K, Schliebs R. Oligomeric beta-amyloid(1–42) induces the expression of Alzheimer disease-relevant proteins in cholinergic SN56.B5.G4 cells as revealed by proteomic analysis. Int J Dev Neurosci 2008;26(3–4):301–308.
Aebersold R, Mann M. Mass spectrometry-based proteomics. Nat. 2003;422(6928):198–207.
Mishra NC, Blobel G, Blobel G. Nter: Introduction to Proteomics: Principles and Applications. Hoboken: John Wiley & Sons, Incorporated; 2010.
Deacon RM. Housing, husbandry and handling of rodents for behavioral experiments. Nat Protoc. 2006;1(2):936–46.
pubmed: 17406327
Fridgeirsdottir GA, Hillered L, Clausen F. Escalated handling of young C57BL/6 mice results in altered Morris water maze performance. Upsala J Med Sci. 2014;119(1):1–9.
pubmed: 24172203
pmcid: 3916711
Sen MK, Mahns DA, Coorssen JR, Shortland PJ. Behavioural phenotypes in the cuprizone model of central nervous system demyelination. Neurosci Biobehav Rev. 2019;107:23–46.
pubmed: 31442519
Sen MK, Almuslehi MSM, Coorssen JR, Mahns DA, Shortland PJ. Behavioural and histological changes in cuprizone-fed mice. Brain Behav Immun. 2020;87:508–23.
pubmed: 32014578
Carter RJ, Morton J, Dunnett SB: Motor coordination and balance in rodents. Curr Protoc Neurosci 2001;Chapter 8:Unit 8.12.
Southwell AL, Ko J, Patterson PH. Intrabody gene therapy ameliorates motor, cognitive, and neuropathological symptoms in multiple mouse models of Huntington’s disease. J Neurosci. 2009;29(43):13589–602.
pubmed: 19864571
pmcid: 2822643
Butt RH, Coorssen JR. Postfractionation for enhanced proteomic analyses: routine electrophoretic methods increase the resolution of standard 2D-PAGE. J Proteome Res. 2005;4(3):982–91.
pubmed: 15952746
Churchward MA, Butt RH, Lang JC, Hsu KK, Coorssen JR. Enhanced detergent extraction for analysis of membrane proteomes by two-dimensional gel electrophoresis. Proteome Sci. 2005;3(1):5–5.
pubmed: 15941475
pmcid: 1184097
Agnew BJ, Murray D, Patton WF. A rapid solid-phase fluorescence-based protein assay for quantitation of protein electrophoresis samples containing detergents, chaotropes, dyes, and reducing agents. Electrophoresis. 2004;25(15):2478–85.
pubmed: 15300765
Stimpson SE, Coorssen JR, Myers SJ. Mitochondrial protein alterations in a familial peripheral neuropathy caused by the V144D amino acid mutation in the sphingolipid protein, SPTLC1. J Chem Biol. 2015;8(1):25–35.
pubmed: 25584079
Wright EP, Prasad KA, Padula MP, Coorssen JR. Deep imaging: how much of the proteome does current top-down technology already resolve? PLoS One 2014;9(1):e86058.
Huang DW, Sherman BT, Tan Q, Kir J, Liu D, Bryant D, Guo Y, Stephens R, Baseler MW, Lane HC, et al. DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res 2007;35:W169–175.
Sherman BT, Huang DW, Tan Q, Guo Y, Bour S, Liu D, Stephens R, Baseler MW, Lane HC, Lempicki RA. DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis. BMC Bioinformatics. 2007;8(1):426.
pubmed: 17980028
pmcid: 2186358
Anderson ME. The role of the cerebellum in motor control and motor learning. Phys Med Rehabil Clin N Am. 1993;4(4):623–36.
Rozas G, Guerra MJ, Labandeira-Garcia JL. An automated rotarod method for quantitative drug-free evaluation of overall motor deficits in rat models of parkinsonism. Brain Res Protoc. 1997;2(1):75–84.
Rustay NR, Wahlsten D, Crabbe JC. Influence of task parameters on rotarod performance and sensitivity to ethanol in mice. Behav Brain Res. 2003;141(2):237–49.
pubmed: 12742261
Shiotsuki H, Yoshimi K, Shimo Y, Funayama M, Takamatsu Y, Ikeda K, Takahashi R, Kitazawa S, Hattori N. A rotarod test for evaluation of motor skill learning. J Neurosci Methods. 2010;189(2):180–5.
pubmed: 20359499
Stanley JL, Lincoln RJ, Brown TA, McDonald LM, Dawson GR, Reynolds DS. The mouse beam walking assay offers improved sensitivity over the mouse rotarod in determining motor coordination deficits induced by benzodiazepines. J Psychopharmacol. 2005;19(3):221–7.
pubmed: 15888506
Probert L, Akassoglou K, Pasparakis M, Kontogeorgos G, Kollias G. Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system-specific expression of tumor necrosis factor alpha. Proc Natl Acad Sci. 1995;92(24):11294–8.
pubmed: 7479982
pmcid: 40618
Bolton JL, Smith SH, Huff NC, Gilmour MI, Foster WM, Auten RL, Bilbo SD. Prenatal air pollution exposure induces neuroinflammation and predisposes offspring to weight gain in adulthood in a sex-specific manner. FASEB J. 2012;26(11):4743–54.
pubmed: 22815382
Mishra D, Richard JE, Maric I, Porteiro B, Häring M, Kooijman S, Musovic S, Eerola K, López-Ferreras L, Peris E, et al. Parabrachial interleukin-6 reduces body weight and food intake and increases thermogenesis to regulate energy metabolism. Cell Rep 2019;26(11):3011-3026.e5.
Stenlöf K, Wernstedt I, Fjällman T, Wallenius V, Wallenius K, Jansson JO. Interleukin-6 levels in the central nervous system are negatively correlated with fat mass in overweight/obese subjects. J Clin Endocrinol Metab. 2003;88(9):4379–83.
pubmed: 12970313
Arevalo JA, Vázquez-Medina JP. The role of peroxiredoxin 6 in cell signaling. Antioxidants. 2018;7(12):172.
pmcid: 6316032
Benson DL, Mandell JW, Shaw G, Banker G. Compartmentation of alpha-internexin and neurofilament triplet proteins in cultured hippocampal neurons. J Neurocytol. 1996;25(1):181–96.
pubmed: 8737171
Kozjak-Pavlovic V. The MICOS complex of human mitochondria. Cell Tissue Res. 2017;367(1):83–93.
pubmed: 27245231
Yuan A, Sershen H, Veeranna, Basavarajappa BS, Kumar A, Hashim A, Berg M, Lee JH, Sato Y, Rao MV, et al. Neurofilament subunits are integral components of synapses and modulate neurotransmission and behavior in vivo. Mol Psychiatry 2015;20(8):986–994.
Friedman JR, Mourier A, Yamada J, McCaffery JM, Nunnari J. MICOS coordinates with respiratory complexes and lipids to establish mitochondrial inner membrane architecture. eLife 2015;4:e07739.
Genin EC, Bannwarth S, Lespinasse F, Ortega-Vila B, Fragaki K, Itoh K, Villa E, Lacas-Gervais S, Jokela M, Auranen M, et al. Loss of MICOS complex integrity and mitochondrial damage, but not TDP-43 mitochondrial localisation, are likely associated with severity of CHCHD10-related diseases. Neurobiol Dis. 2018;119:159–71.
pubmed: 30092269
pmcid: 7015038
Myers SJ, Malladi CS, Hyland RA, Bautista T, Boadle R, Robinson PJ, Nicholson GA. Mutations in the SPTLC1 protein cause mitochondrial structural abnormalities and endoplasmic reticulum stress in lymphoblasts. DNA Cell Biol. 2014;33(7):399–407.
pubmed: 24673574
Sukonina V, Ma H, Zhang W, Bartesaghi S, Subhash S, Heglind M, Foyn H, Betz MJ, Nilsson D, Lidell ME, et al. FOXK1 and FOXK2 regulate aerobic glycolysis. Nat. 2019;566(7743):279–83.
Fox GB, Faden AI. Traumatic brain injury causes delayed motor and cognitive impairment in a mutant mouse strain known to exhibit delayed wallerian degeneration. J Neurosci Res. 1998;53(6):718–27.
pubmed: 9753199
Hill CS, Coleman MP, Menon DK. Traumatic Axonal injury: mechanisms and translational opportunities. Trends Neurosci. 2016;39(5):311–24.
pubmed: 27040729
pmcid: 5405046
Kiyosawa K, Mokuno K, Murakami N, Yasuda T, Kume A, Hashizume Y, Takahashi A, Kato K. Cerebrospinal fluid 28-kDa calbindin-D as a possible marker for Purkinje cell damage. J Neurol Sci. 1993;118(1):29–33.
pubmed: 8229048
Childs R, Gamage R, Munch G, Gyengesi E. The effect of aging and chronic microglia activation on the morphology and numbers of the cerebellar Purkinje cells. Neurosci Letters. 2021;751:135807.
Spooren A, Kolmus K, Laureys G, Clinckers R, De Keyser J, Haegeman G, Gerlo S. Interleukin-6, a mental cytokine. Brain Res Rev. 2011;67(1):157–83.
pubmed: 21238488
Chiou B, Neely EB, Mcdevitt DS, Simpson IA, Connor JR. Transferrin and H-ferritin involvement in brain iron acquisition during postnatal development: impact of sex and genotype. J Neurochem. 2020;152(3):381–96.
pubmed: 31339576
Rose-John S, Scheller J, Elson G, Jones SA. Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J Leukoc Biol. 2006;80(2):227–36.
pubmed: 16707558
Campbell IL, Erta M, Lim SL, Frausto R, May U, Rose-John S, Scheller J, Hidalgo J. Trans-signaling is a dominant mechanism for the pathogenic actions of interleukin-6 in the brain. J Neurosci. 2014;34(7):2503–13.
pubmed: 24523541
pmcid: 6802757
Willis EF, MacDonald KPA, Nguyen QH, Garrido AL, Gillespie ER, Harley SBR, Bartlett PF, Schroder WA, Yates AG, Anthony DC, et al. Repopulating Microglia promote brain repair in an IL-6-dependent manner. Cell 2020;180(5):833-846.e16.
Penkowa M, Camats J, Hadberg H, Quintana A, Rojas S, Giralt M, Molinero A, Campbell IL, Hidalgo J. Astrocyte-targeted expression of interleukin-6 protects the central nervous system during neuroglial degeneration induced by 6-aminonicotinamide. J Neurosci Res. 2003;73(4):481–96.
pubmed: 12898533
Loddick SA, Turnbull AV, Rothwell NJ. Cerebral interleukin-6 is neuroprotective during permanent focal cerebral ischemia in the rat. J Cereb Blood Flow Metab. 1998;18(2):176–9.
pubmed: 9469160
Toulmond S, Vige X, Fage D, Benavides J. Local infusion of interleukin-6 attenuates the neurotoxic effects of NMDA on rat striatal cholinergic neurons. Neurosci Letters. 1992;144(1–2):49–52.
Bachiller S, Jiménez-Ferrer I, Paulus A, Yang Y, Swanberg M, Deierborg T, Boza-Serrano A. Microglia in neurological diseases: a road map to brain-disease dependent-inflammatory response. Front Cell Neurosci 2018;12:488.
Hanisch U-K. Functional diversity of microglia – how heterogeneous are they to begin with? Front Cell Neurosci 2013;7:65.
Bowen KK, Dempsey RJ, Vemuganti R. Adult interleukin-6 knockout mice show compromised neurogenesis. Neuroreport. 2011;22(3):126–30.
pubmed: 21266900
Penkowa M, Moos T, Carrasco J, Hadberg H, Molinero A, Bluethmann H, Hidalgo J. Strongly compromised inflammatory response to brain injury in interleukin-6-deficient mice. Glia. 1999;25(4):343–57.
pubmed: 10028917
Braida D, Sacerdote P, Panerai AE, Bianchi M, Aloisi AM, Iosuè S, Sala M. Cognitive function in young and adult IL (interleukin)-6 deficient mice. Behav Brain Res. 2004;153(2):423–9.
pubmed: 15265638
Chourbaji S, Urani A, Inta I, Sanchis-Segura C, Brandwein C, Zink M, Schwaninger M, Gass P. IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors. Neurobiol Dis. 2006;23(3):587–94.
pubmed: 16843000
Hryniewicz A, Bialuk I, Kamiński KA, Winnicka MM. Impairment of recognition memory in interleukin-6 knock-out mice. Eur J Pharmacol. 2007;577(1–3):219–20.
pubmed: 17920057
Garbis S, Lubec G, Fountoulakis M. Limitations of current proteomics technologies. J Chromatogr A. 2005;1077(1):1–18.
pubmed: 15988981
Chitta MS, Duhé RJ, Kermode JC. Cloning of the cDNA for murine von Willebrand factor and identification of orthologous genes reveals the extent of conservation among diverse species. Platelets. 2007;18(3):182–98.
pubmed: 17497430
Maier B, Tersey SA, Mirmira RG. Hypusine: a new target for therapeutic intervention in diabetic inflammation. Discov Med. 2010;10(50):18–23.
pubmed: 20670594
Moore CC, Martin EN, Lee G, Taylor C, Dondero R, Reznikov LL, Dinarello C, Thompson J, Scheld WM. Eukaryotic translation initiation factor 5A small interference RNA-liposome complexes reduce inflammation and increase survival in murine models of severe sepsis and acute lung injury. J Infect Dis. 2008;198(9):1407–14.
pubmed: 18793104
Mergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci. 2013;36(10):587–97.
pubmed: 23968694
pmcid: 3900881
Giri S, Suhail H, Singh J, Kumar A, Rattan R. Early burst of glycolysis in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuro-inflammation. J Immunol 2018;200:49.16.
Jayasena T, Poljak A, Braidy N, Smythe G, Raftery M, Hill M, Brodaty H, Trollor J, Kochan N, Sachdev P. Upregulation of glycolytic enzymes, mitochondrial dysfunction and increased cytotoxicity in glial cells treated with Alzheimer’s disease plasma. PloS One 2015;10(3):e0116092.
Rhein V, Song X, Wiesner A, Ittner LM, Baysang G, Meier F, Ozmen L, Bluethmann H, Dröse S. Brandt U et al. Amyloid-β and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer’s disease mice. Proc Natl Acad Sci. 2009;106(47):20057–62.
Nelson DL, Cox MM, Lehninger AL: Lehninger Principles of Biochemistry; 2017. 5
Moreira PI, Carvalho C, Zhu X, Smith MA, Perry G. Mitochondrial dysfunction is a trigger of Alzheimer’s disease pathophysiology. BBA. 2010;1802(1):2–10.
pubmed: 19853658
Swerdlow RH. Mitochondria and mitochondrial cascades in Alzheimer’s disease. J Alzheimers Dis. 2018;62(3):1403–16.
pubmed: 29036828
pmcid: 5869994
Ellis RJ. The molecular chaperone concept. Semin Cell Biol. 1990;1(1):1–9.
pubmed: 1983265
Huang Q, Figueiredo-Pereira ME. Ubiquitin/proteasome pathway impairment in neurodegeneration: therapeutic implications. Apoptosis. 2010;15(11):1292–311.
pubmed: 20131003
pmcid: 2908192
van Noort J. Stress proteins in CNS inflammation. J Pathol. 2008;214(2):267–75.
pubmed: 18161755
Keck S, Nitsch R, Grune T, Ullrich O. Proteasome inhibition by paired helical filament-tau in brains of patients with Alzheimer’s disease. J Neurochem. 2003;85(1):115–22.
pubmed: 12641733
Zabel C, Nguyen HP, Hin SC, Hartl D, Mao L, Klose J. Proteasome and oxidative phoshorylation changes may explain why aging is a risk factor for neurodegenerative disorders. J Proteomics. 2010;73(11):2230–8.
pubmed: 20813214
McClellan AJ, Frydman J. Molecular chaperones and the art of recognizing a lost cause. Nat Cell Biol 2001;3(2):E51-53.
Figueiredo-Pereira ME, Rockwell P, Schmidt-Glenewinkel T, Serrano P. Neuroinflammation and J2 prostaglandins: linking impairment of the ubiquitin-proteasome pathway and mitochondria to neurodegeneration. Front Mol Neurosci 2015;7:104.
Perry G, Friedman R, Shaw G, Chau V. Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. Proc Natl Acad Sci. 1987;84(9):3033–6.
pubmed: 3033674
pmcid: 304795
Janke C, Kneussel M. Tubulin post-translational modifications: encoding functions on the neuronal microtubule cytoskeleton. Trends Neurosci. 2010;33(8):362–72.
pubmed: 20541813
Guzhova I, Kislyakova K, Moskaliova O, Fridlanskaya I, Tytell M, Cheetham M, Margulis B. In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance. Brain Res. 2001;914(1–2):66–73.
pubmed: 11578598
Lancaster GI, Febbraio MA. Exosome-dependent trafficking of HSP70: a novel secretory pathway for cellular stress proteins. J Biol Chem. 2005;280(24):23349–55.
pubmed: 15826944
Fisher AB. Peroxiredoxin 6: a bifunctional enzyme with glutathione peroxidase and phospholipase A(2) activities. Antioxid Redox Signal. 2011;15(3):831–44.
pubmed: 20919932
pmcid: 3125547
Sorokina EM, Feinstein SI, Zhou S, Fisher AB. Intracellular targeting of peroxiredoxin 6 to lysosomal organelles requires MAPK activity and binding to 14-3-3ε. Am J Physiol Cell Physiol. 2011;300(6):1430–41.
D’Silva AM, Hyett JA, Coorssen JR. Proteomic analysis of first trimester maternal serum to identify candidate biomarkers potentially predictive of spontaneous preterm birth. J Proteomics. 2018;178:31–42.
pubmed: 29448056