1,184
Views
2
CrossRef citations to date
0
Altmetric
Review

The beneficial role of autophagy in multiple sclerosis: Yes or No?

, , , ORCID Icon, & ORCID Icon
Pages 259-274 | Received 01 May 2023, Accepted 08 Sep 2023, Published online: 25 Sep 2023

References

  • Dobson R, Giovannoni G. Multiple sclerosis–a review. European journal of neurology. 2019;26(1):27–40.
  • Kumar DR, Aslinia F, Yale SH, et al. Jean-Martin Charcot: the father of neurology. Clinical medicine & research. 2011;9(1):46–49.
  • Olsson T, Barcellos LF, Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nature Reviews Neurology. 2017;13(1):25–36.
  • Massey J, Jackson K, Singh M, et al. Haematopoietic stem cell transplantation results in extensive remodelling of the clonal T cell repertoire in multiple sclerosis. Frontiers in Immunology. 2022;13:798300.
  • Balasa R, Barcutean L, Mosora O, et al. Reviewing the significance of blood–brain barrier disruption in multiple sclerosis pathology and treatment. International Journal of Molecular Sciences. 2021;22(16):8370.
  • Mohammadhosayni M, Khosrojerdi A, Lorian K, et al. Matrix metalloproteinases (MMPs) family gene polymorphisms and the risk of multiple sclerosis: systematic review and meta-analysis. BMC neurology. 2020;20:1–10.
  • Höftberger R, Lassmann H, Berger T, et al. Pathogenic autoantibodies in multiple sclerosis—from a simple idea to a complex concept. Nature Reviews Neurology. 2022;18(11):681–688.
  • Chihara N. Dysregulated T cells in multiple sclerosis. Clinical and Experimental Neuroimmunology. 2018;9:20–29.
  • Dziedzic A, Miller E, Saluk-Bijak J, et al. The GPR17 receptor—a promising goal for therapy and a potential marker of the neurodegenerative process in multiple sclerosis. International journal of molecular sciences. 2020;21(5):1852.
  • Kennedy PG, George W, Yu X. The possible role of neural cell apoptosis in multiple sclerosis. International Journal of Molecular Sciences. 2022;23(14):7584.
  • Melchor GS, Khan T, Reger JF, et al. Remyelination pharmacotherapy investigations highlight diverse mechanisms underlying multiple sclerosis progression. ACS Pharmacology & Translational Science. 2019;2(6):372–386.
  • Abdalla MA, Zakhary CM, Rushdi H, et al. The effectiveness of statins as potential therapy for multiple sclerosis: a systematic review of randomized controlled trials. Cureus. 2021;13(9).
  • Kenyon KA, Bushong EA, Mauer AS, et al. Cellular and subcellular localization of the neuron‐specific plasma membrane calcium ATPase PMCA1a in the rat brain. Journal of Comparative Neurology. 2010;518(16):3169–3183.
  • Lee J-A. Neuronal autophagy: a housekeeper or a fighter in neuronal cell survival? Experimental neurobiology. 2012;21(1):1.
  • Misrielal C, Mauthe M, Reggiori F, et al. Autophagy in multiple sclerosis: two sides of the same coin. Frontiers in cellular neuroscience. 2020;14:603710.
  • Ktistakis NT. In praise of M. Anselmier who first used the term “autophagie” in 1859. Taylor & Francis; 2017. p. 2015–2017.
  • Klionsky DJ. Autophagy revisited: a conversation with Christian de Duve. Autophagy. 2008;4(6):740–743.
  • Klionsky DJ, Cueva R, Yaver DS. Aminopeptidase I of Saccharomyces cerevisiae is localized to the vacuole independent of the secretory pathway. The Journal of cell biology. 1992;119(2):287–299.
  • Harding TM, Morano KA, Scott SV, et al. Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway. The Journal of cell biology. 1995;131(3):591–602.
  • Li X, He S, Ma B. Autophagy and autophagy-related proteins in cancer. Molecular cancer. 2020;19(1):1–16.
  • Abdrakhmanov A, Gogvadze V, Zhivotovsky B. To eat or to die: deciphering selective forms of autophagy. Trends in biochemical sciences. 2020;45(4):347–364.
  • Rong Y, McPhee CK, Deng S, et al. Spinster is required for autophagic lysosome reformation and mTOR reactivation following starvation. Proceedings of the National Academy of Sciences. 2011;108(19):7826–7831.
  • Chen Q, Shinozaki D, Luo J, et al. Autophagy and nutrients management in plants. Cells. 2019;8(11):1426.
  • Yuan Z, Wang S, Tan X, et al. New insights into the mechanisms of chaperon-mediated autophagy and implications for kidney diseases. Cells. 2022;11(3):406.
  • Kaushik S, Cuervo AM. The coming of age of chaperone-mediated autophagy. Nature reviews Molecular cell biology. 2018;19(6):365–381.
  • Vicencio E, Beltrán S, Labrador L, et al. Implications of selective autophagy dysfunction for ALS pathology. Cells. 2020;9(2):381.
  • Kojima W, Yamano K, Kosako H, et al. Mammalian BCAS3 and C16orf70 associate with the phagophore assembly site in response to selective and non-selective autophagy. Autophagy. 2021;17(8):2011–2036.
  • Zaffagnini G, Martens S. Mechanisms of selective autophagy. Journal of molecular biology. 2016;428(9):1714–1724.
  • Lei Y, Klionsky DJ. The coordination of V-ATPase and ATG16L1 is part of a common mechanism of non-canonical autophagy. Taylor & Francis; 2022. p. 2267–2269.
  • Herb M, Gluschko A, Schramm M, editors. LC3-associated phagocytosis-The highway to hell for phagocytosed microbes. Seminars in cell & developmental biology; 2020: Elsevier.
  • Martinez J, Almendinger J, Oberst A, et al. Microtubule-associated protein 1 light chain 3 alpha (LC3)-associated phagocytosis is required for the efficient clearance of dead cells. Proceedings of the National Academy of Sciences. 2011;108(42):17396–17401.
  • Heckmann BL, Teubner BJ, Tummers B, et al. LC3-associated endocytosis facilitates β-amyloid clearance and mitigates neurodegeneration in murine Alzheimer’s disease. Cell. 2019;178(3):536–551. e14.
  • Sahu R, Kaushik S, Clement CC, et al. Microautophagy of cytosolic proteins by late endosomes. Developmental cell. 2011;20(1):131–139.
  • Solvik TA, Nguyen TA, Tony Lin Y-H, et al. Secretory autophagy maintains proteostasis upon lysosome inhibition. Journal of Cell Biology. 2022;221(6):e202110151.
  • Keller CW, Lünemann JD. Autophagy and autophagy-related proteins in CNS autoimmunity. Frontiers in immunology. 2017;8:165.
  • Klionsky DJ, Petroni G, Amaravadi RK, et al. Autophagy in major human diseases. The EMBO journal. 2021;40(19):e108863.
  • Kondratskyi A, Kondratska K, Skryma R, et al. Ion channels in the regulation of autophagy. Autophagy. 2018;14(1):3–21.
  • Wu Y, Zhang J, Li Q. Autophagy, an accomplice or antagonist of drug resistance in HCC? Cell Death & Disease. 2021;12(3):266.
  • Nascimbeni AC, Codogno P, Morel E. Phosphatidylinositol‐3‐phosphate in the regulation of autophagy membrane dynamics. The FEBS journal. 2017;284(9):1267–1278.
  • Nixon RA. The role of autophagy in neurodegenerative disease. Nature medicine. 2013;19(8):983–997.
  • Menzies FM, Fleming A, Rubinsztein DC. Compromised autophagy and neurodegenerative diseases. Nature Reviews Neuroscience. 2015;16(6):345–357.
  • Son JH, Shim JH, Kim K-H, et al. Neuronal autophagy and neurodegenerative diseases. Experimental & molecular medicine. 2012;44(2):89–98.
  • Castellazzi M, Patergnani S, Donadio M, et al. Autophagy and mitophagy biomarkers are reduced in sera of patients with Alzheimer’s disease and mild cognitive impairment. Scientific reports. 2019;9(1):20009.
  • Al‐kuraishy HM, Al‐Gareeb AI, Kaushik A, et al. SARS‐COV‐2 infection and Parkinson’s disease: Possible links and perspectives. Journal of Neuroscience Research. 2023;101(6):952–975.
  • Al‐kuraishy HM, Al‐Gareeb AI, Alexiou A, et al. Pros and cons for statins use and risk of Parkinson’s disease: An updated perspective. Pharmacology Research & Perspectives. 2023;11(2):e01063.
  • Yan J-q, Yuan Y-h, Chu S-f, et al. E46K mutant α-synuclein is degraded by both proteasome and macroautophagy pathway. Molecules. 2018;23(11):2839.
  • Vogiatzi T, Xilouri M, Vekrellis K, et al. Wild type α-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. Journal of Biological Chemistry. 2008;283(35):23542–23556.
  • Bae E-J, Lee S-J. The LRRK2-RAB axis in regulation of vesicle trafficking and α-synuclein propagation. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2020;1866(3):165632.
  • Tong Y, Giaime E, Yamaguchi H, et al. Loss of leucine-rich repeat kinase 2 causes age-dependent bi-phasic alterations of the autophagy pathway. Molecular neurodegeneration. 2012;7(1):1–16.
  • Alfaro IE, Albornoz A, Molina A, et al. Chaperone mediated autophagy in the crosstalk of neurodegenerative diseases and metabolic disorders. Frontiers in Endocrinology. 2019;9:778.
  • Choi KC, Kim SH, Ha JY, et al. A novel mTOR activating protein protects dopamine neurons against oxidative stress by repressing autophagy related cell death. Journal of neurochemistry. 2010;112(2):366–376.
  • Kriel J, Loos B. The good, the bad and the autophagosome: exploring unanswered questions of autophagy-dependent cell death. Cell Death & Differentiation. 2019;26(4):640–652.
  • Malpartida AB, Williamson M, Narendra DP, et al. Mitochondrial dysfunction and mitophagy in Parkinson’s disease: from mechanism to therapy. Trends in biochemical sciences. 2021;46(4):329–343.
  • Youn J, Lee S-B, Lee HS, et al. Cerebrospinal fluid levels of autophagy-related proteins represent potentially novel biomarkers of early-stage Parkinson’s disease. Scientific Reports. 2018;8(1):16866.
  • Prigione A, Piazza F, Brighina L, et al. Alpha-synuclein nitration and autophagy response are induced in peripheral blood cells from patients with Parkinson disease. Neuroscience letters. 2010;477(1):6–10.
  • Kang J, Kim JW, Heo H, et al. Identification of BAG2 and cathepsin D as plasma biomarkers for Parkinson’s disease. Clinical and Translational Science. 2021;14(2):606–616.
  • Papagiannakis N, Stefanis L. Autophagy-lysosome pathway as a source of candidate biomarkers for Parkinson’s disease. Neuroimmunology and Neuroinflammation. 2021;8(2):101–110.
  • Alsubaie N, Al-Kuraishy HM, Al-Gareeb AI, et al. Statins use in Alzheimer disease: bane or boon from frantic search and narrative review. Brain Sciences. 2022;12(10):1290.
  • Al-Kuraishy HM, Al-Gareeb AI, Alsayegh AA, et al. A potential link between visceral obesity and risk of Alzheimer’s disease. Neurochemical Research. 2023;48(3):745–766.
  • Al-Kuraishy HM, Al-Gareeb AI, Saad HM, et al. Benzodiazepines in Alzheimer’s disease: beneficial or detrimental effects. Inflammopharmacology. 2023;31(1):221–230.
  • Al-Kuraishy HM, Al-Gareeb AI, Alsayegh AA, et al. Insights on benzodiazepines’ potential in Alzheimer’s disease. Life Sciences. 2023:121532.
  • Al-Kuraishy HM, Al-Gareeb AI, Saad HM, et al. Long-term use of metformin and Alzheimer’s disease: beneficial or detrimental effects. Inflammopharmacology. 2023:1–9.
  • Nixon RA, Wegiel J, Kumar A, et al. Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. Journal of Neuropathology & Experimental Neurology. 2005;64(2):113–122.
  • Yu WH, Cuervo AM, Kumar A, et al. Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer’s disease. The Journal of cell biology. 2005;171(1):87–98.
  • Perluigi M, Di Domenico F, Barone E, et al. mTOR in Alzheimer disease and its earlier stages: Links to oxidative damage in the progression of this dementing disorder. Free Radical Biology and Medicine. 2021;169:382–396.
  • Estfanous S, Daily KP, Eltobgy M, et al. Elevated expression of MiR-17 in microglia of Alzheimer’s disease patients abrogates autophagy-mediated amyloid-β degradation. Frontiers in immunology. 2021;12:705581.
  • Khandelwal PJ, Herman AM, Hoe H-S, et al. Parkin mediates beclin-dependent autophagic clearance of defective mitochondria and ubiquitinated Aβ in AD models. Human molecular genetics. 2011;20(11):2091–2102.
  • Kou X, Chen D, Chen N. The regulation of microRNAs in Alzheimer’s disease. Frontiers in Neurology. 2020;11:288.
  • Boland B, Kumar A, Lee S, et al. Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease. Journal of Neuroscience. 2008;28(27):6926–6937.
  • Lee J-H, Yu WH, Kumar A, et al. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell. 2010;141(7):1146–1158.
  • Sepe S, Nardacci R, Fanelli F, et al. Expression of Ambra1 in mouse brain during physiological and Alzheimer type aging. Neurobiology of Aging. 2014;35(1):96–108.
  • Feldman EL, Goutman SA, Petri S, et al. Amyotrophic lateral sclerosis. The Lancet. 2022;400(10360):1363–1380.
  • Amin A, Perera ND, Beart PM, et al. Amyotrophic lateral sclerosis and autophagy: dysfunction and therapeutic targeting. Cells. 2020;9(11):2413.
  • Bicchi I, Morena F, Argentati C, et al. Storage of mutant human sod1 in non-neural cells from the type-1 amyotrophic lateral sclerosis ratg93a model correlated with the lysosomes’ dysfunction. Biomedicines. 2021;9(9):1080.
  • Chen S, Zhang X, Song L, et al. Autophagy dysregulation in amyotrophic lateral sclerosis. Brain pathology. 2012;22(1):110–116.
  • Toth RP, Atkin JD. Dysfunction of optineurin in amyotrophic lateral sclerosis and glaucoma. Frontiers in immunology. 2018;9:1017.
  • Maruyama H, Morino H, Ito H, et al. Mutations of optineurin in amyotrophic lateral sclerosis. Nature. 2010;465(7295):223–226.
  • Maruyama H, Kawakami H. Optineurin and amyotrophic lateral sclerosis. Geriatrics & gerontology international. 2013;13(3):528–532.
  • Pasquali L, Longone P, Isidoro C, et al. Autophagy, lithium, and amyotrophic lateral sclerosis. Muscle & Nerve: Official Journal of the American Association of Electrodiagnostic Medicine. 2009;40(2):173–194.
  • Deng Z, Sheehan P, Chen S, et al. Is amyotrophic lateral sclerosis/frontotemporal dementia an autophagy disease? Molecular neurodegeneration. 2017;12:1–11.
  • Hassanpour M, Hajihassani F, Hiradfar A, et al. Real-state of autophagy signaling pathway in neurodegenerative disease; focus on multiple sclerosis. Journal of Inflammation. 2020;17(1):1–8.
  • Liang P, Le W. Role of autophagy in the pathogenesis of multiple sclerosis. Neuroscience bulletin. 2015;31:435–444.
  • Igci M, Baysan M, Yigiter R, et al. Gene expression profiles of autophagy-related genes in multiple sclerosis. Gene. 2016;588(1):38–46.
  • Haider L, Fischer MT, Frischer JM, et al. Oxidative damage in multiple sclerosis lesions. Brain. 2011;134(7):1914–1924.
  • Jang SY, Shin YK, Park SY, et al. Autophagic myelin destruction by Schwann cells during Wallerian degeneration and segmental demyelination. Glia. 2016;64(5):730–742.
  • Mammana S, Bramanti P, Mazzon E, et al. Preclinical evaluation of the PI3K/Akt/mTOR pathway in animal models of multiple sclerosis. Oncotarget. 2018;9(9):8263.
  • Dello Russo C, Lisi L, Feinstein DL, et al. mTOR kinase, a key player in the regulation of glial functions: relevance for the therapy of multiple sclerosis. Glia. 2013;61(3):301–311.
  • Andhavarapu S, Mubariz F, Arvas M, et al. Interplay between ER stress and autophagy: a possible mechanism in multiple sclerosis pathology. Experimental and molecular pathology. 2019;108:183–190.
  • Stone S, Lin W. The unfolded protein response in multiple sclerosis. Frontiers in neuroscience. 2015;9:264.
  • Lin W, Stone S. Unfolded protein response in myelin disorders. Neural regeneration research. 2020;15(4):636.
  • Sato S, Uchihara T, Fukuda T, et al. Loss of autophagy in dopaminergic neurons causes Lewy pathology and motor dysfunction in aged mice. Scientific reports. 2018;8(1):2813.
  • Astier AL, Meiffren G, Freeman S, et al. Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis. The Journal of clinical investigation. 2006;116(12):3252–3257.
  • Di Rita A, Angelini DF, Maiorino T, et al. Characterization of a natural variant of human NDP52 and its functional consequences on mitophagy. Cell Death & Differentiation. 2021;28(8):2499–2516.
  • Kazlauskaite A, Kondapalli C, Gourlay R, et al. Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65. Biochemical Journal. 2014;460(1):127–141.
  • Padman BS, Nguyen TN, Uoselis L, et al. LC3/GABARAPs drive ubiquitin-independent recruitment of Optineurin and NDP52 to amplify mitophagy. Nature communications. 2019;10(1):408.
  • Chen M, Yang L-L, Hu Z-W, et al. Deficiency of microglial Hv1 channel is associated with activation of autophagic pathway and ROS production in LPC-induced demyelination mouse model. Journal of Neuroinflammation. 2020;17:1–12.
  • Alirezaei M, Fox HS, Flynn CT, et al. Elevated ATG5 expression in autoimmune demyelination and multiple sclerosis. Autophagy. 2009;5(2):152–158.
  • Yin L, Liu J, Dong H, et al. Autophagy-related gene16L2, a potential serum biomarker of multiple sclerosis evaluated by bead-based proteomic technology. Neuroscience letters. 2014;562:34–38.
  • Feng X, Hou H, Zou Y, et al. Defective autophagy is associated with neuronal injury in a mouse model of multiple sclerosis. Bosnian Journal of Basic Medical Sciences. 2017;17(2):95.
  • Patergnani S, Bonora M, Ingusci S, et al. Antipsychotic drugs counteract autophagy and mitophagy in multiple sclerosis. Proceedings of the National Academy of Sciences. 2021;118(24):e2020078118.
  • Shen D, Liu K, Wang H, et al. Autophagy modulation in multiple sclerosis and experimental autoimmune encephalomyelitis. Clinical and Experimental Immunology. 2022;209(2):140–150.
  • Castellazzi M, Patergnani S, Donadio M, et al. Correlation between auto/mitophagic processes and magnetic resonance imaging activity in multiple sclerosis patients. Journal of neuroinflammation. 2019;16:1–8.
  • Nourazarian A, Khaki‐Khatibi F, Nikanfar M, et al. Evaluation of the diagnostic and predictive value of serum levels of ANT1, ATG5, and Parkin in multiple sclerosis. Clinical Neurology and Neurosurgery. 2020;197:106197.
  • Qin C, Liu Q, Hu Z-W, et al. Microglial TLR4-dependent autophagy induces ischemic white matter damage via STAT1/6 pathway. Theranostics. 2018;8(19):5434.
  • Hassanpour M, Cheraghi O, Laghusi D, et al. The relationship between ANT1 and NFL with autophagy and mitophagy markers in patients with multiple sclerosis. Journal of Clinical Neuroscience. 2020;78:307–312.
  • Gold R, Linington C, Lassmann H. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain. 2006;129(8):1953–1971.
  • Baxter AG. The origin and application of experimental autoimmune encephalomyelitis. Nature Reviews Immunology. 2007;7(11):904–912.
  • Constantinescu CS, Farooqi N, O’Brien K, et al. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). British journal of pharmacology. 2011;164(4):1079–1106.
  • Brambilla R. The contribution of astrocytes to the neuroinflammatory response in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta neuropathologica. 2019;137(5):757–783.
  • Baker D, Amor S. Experimental autoimmune encephalomyelitis is a good model of multiple sclerosis if used wisely. Multiple sclerosis and related disorders. 2014;3(5):555–564.
  • Haidar M, Loix M, Vanherle S, et al. Targeting lipophagy in macrophages improves repair in multiple sclerosis. Autophagy. 2022;18(11):2697–2710.
  • Boyao Y, Mengjiao S, Caicai B, et al. Dynamic expression of autophagy-related factors in autoimmune encephalomyelitis and exploration of curcumin therapy. Journal of Neuroimmunology. 2019;337:577067.
  • Bruzzone S, Fruscione F, Morando S, et al. Catastrophic NAD+ depletion in activated T lymphocytes through Nampt inhibition reduces demyelination and disability in EAE. PloS one. 2009;4(11):e7897.
  • Manuse MJ, Briggs CM, Parks GD. Replication-independent activation of human plasmacytoid dendritic cells by the paramyxovirus SV5 Requires TLR7 and autophagy pathways. Virology. 2010;405(2):383–389.
  • Ravikumar B, Vacher C, Berger Z, et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nature genetics. 2004;36(6):585–595.
  • Wang X, Li B, Liu L, et al. Nicotinamide adenine dinucleotide treatment alleviates the symptoms of experimental autoimmune encephalomyelitis by activating autophagy and inhibiting the NLRP3 inflammasome. International Immunopharmacology. 2021;90:107092.
  • Bhattacharya A, Parillon X, Zeng S, et al. Deficiency of autophagy in dendritic cells protects against experimental autoimmune encephalomyelitis. Journal of Biological Chemistry. 2014;289(38):26525–26532.
  • Andersson Å, Covacu R, Sunnemark D, et al. Pivotal advance: HMGB1 expression in active lesions of human and experimental multiple sclerosis. Journal of Leucocyte Biology. 2008;84(5):1248–1255.
  • Di Rita A, Strappazzon F. A protective variant of the autophagy receptor CALCOCO2/NDP52 in Multiple Sclerosis (MS). Autophagy. 2021;17(6):1565–1567.
  • Leidal AM, Levine B, Debnath J. Autophagy and the cell biology of age-related disease. Nature cell biology. 2018;20(12):1338–1348.
  • Rangaraju S, Verrier JD, Madorsky I, et al. Rapamycin activates autophagy and improves myelination in explant cultures from neuropathic mice. Journal of Neuroscience. 2010;30(34):11388–11397.
  • Sanjuan MA, Dillon CP, Tait SW, et al. Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature. 2007;450(7173):1253–1257.
  • Meikle L, Pollizzi K, Egnor A, et al. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. Journal of Neuroscience. 2008;28(21):5422–5432.
  • David MA, Tayebi M. Detection of protein aggregates in brain and cerebrospinal fluid derived from multiple sclerosis patients. Frontiers in neurology. 2014;5:251.
  • Albert M, Barrantes‐Freer A, Lohrberg M, et al. Synaptic pathology in the cerebellar dentate nucleus in chronic multiple sclerosis. Brain Pathology. 2017;27(6):737–747.
  • Zirngibl M, Assinck P, Sizov A, et al. Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination. Molecular Neurodegeneration. 2022;17(1):1–28.
  • Clarke LE, Liddelow SA, Chakraborty C, et al. Normal aging induces A1-like astrocyte reactivity. Proceedings of the National Academy of Sciences. 2018;115(8):E1896–E1905.
  • Guerrero B, Sicotte N. Microglia in multiple sclerosis: friend or foe? Front Immunol 11: 374. 2020.
  • Ghislat G, Lawrence T. Autophagy in dendritic cells. Cellular & molecular immunology. 2018;15(11):944–952.
  • Nalbandian A, Llewellyn KJ, Nguyen C, et al. Rapamycin and chloroquine: the in vitro and in vivo effects of autophagy-modifying drugs show promising results in valosin containing protein multisystem proteinopathy. PLoS One. 2015;10(4):e0122888.
  • Riccio P, Rossano R. Nutrition facts in multiple sclerosis. ASN Neuro, 7 (1), 1759091414568185. 2015.
  • Fanara S, Aprile M, Iacono S, et al. The role of nutritional lifestyle and physical activity in multiple sclerosis pathogenesis and management: a narrative review. Nutrients. 2021;13(11):3774.
  • Fitzgerald KC, Vizthum D, Henry-Barron B, et al. Effect of intermittent vs. daily calorie restriction on changes in weight and patient-reported outcomes in people with multiple sclerosis. Multiple sclerosis and related disorders. 2018;23:33–39.
  • Collett J, Dawes H, Meaney A, et al. Exercise for multiple sclerosis: a single-blind randomized trial comparing three exercise intensities. Multiple sclerosis journal. 2011;17(5):594–603.
  • Bharath LP, Agrawal M, McCambridge G, et al. Metformin enhances autophagy and normalizes mitochondrial function to alleviate aging-associated inflammation. Cell metabolism. 2020;32(1):44–55. e6.
  • Dziedzic A, Saluk-Bijak J, Miller E, et al. Metformin as a potential agent in the treatment of multiple sclerosis. International Journal of Molecular Sciences. 2020;21(17):5957.
  • Nath N, Khan M, Paintlia MK, et al. Metformin attenuated the autoimmune disease of the central nervous system in animal models of multiple sclerosis. The Journal of Immunology. 2009;182(12):8005–8014.
  • Largani SHH, Borhani-Haghighi M, Pasbakhsh P, et al. Oligoprotective effect of metformin through the AMPK-dependent on restoration of mitochondrial hemostasis in the cuprizone-induced multiple sclerosis model. Journal of Molecular Histology. 2019;50:263–271.
  • Negrotto L, Farez MF, Correale J. Immunologic effects of metformin and pioglitazone treatment on metabolic syndrome and multiple sclerosis. JAMA neurology. 2016;73(5):520–528.
  • Melrose J, Hayes AJ, Bix G. The CNS/PNS extracellular matrix provides instructive guidance cues to neural cells and neuroregulatory proteins in neural development and repair. International Journal of Molecular Sciences. 2021;22(11):5583.
  • Toomey LM, Papini MG, Clarke TO, et al. Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats. International Journal of Molecular Sciences. 2023;24(4):3463.
  • Fernandes MGF, Luo JXX, Cui Q-L, et al. Age-related injury responses of human oligodendrocytes to metabolic insults: link to BCL-2 and autophagy pathways. Communications Biology. 2021;4(1):20.
  • Wang M-R, Zhang X-J, Liu H-C, et al. Matrine protects oligodendrocytes by inhibiting their apoptosis and enhancing mitochondrial autophagy. Brain Research Bulletin. 2019;153:30–38.
  • Agliardi C, Guerini FR, Zanzottera M, et al. Myelin basic protein in oligodendrocyte-derived extracellular vesicles as a diagnostic and prognostic biomarker in multiple sclerosis: a pilot study. International Journal of Molecular Sciences. 2023;24(1):894.
  • Chen Y, Zhang Z-X, Zheng L-P, et al. The adenosine A2A receptor antagonist SCH58261 reduces macrophage/microglia activation and protects against experimental autoimmune encephalomyelitis in mice. Neurochemistry International. 2019;129:104490.
  • Aboul-Enein F, Weiser P, Höftberger R, et al. Transient axonal injury in the absence of demyelination: a correlate of clinical disease in acute experimental autoimmune encephalomyelitis. Acta neuropathologica. 2006;111:539–547.
  • Paunovic V, Petrovic IV, Milenkovic M, et al. Autophagy-independent increase of ATG5 expression in T cells of multiple sclerosis patients. Journal of Neuroimmunology. 2018;319:100–105.
  • Yang Z, Goronzy JJ, Weyand CM. Autophagy in autoimmune disease. Journal of molecular medicine. 2015;93:707–717.
  • Yang G, Song W, Postoak JL, et al. Autophagy-related protein PIK3C3/VPS34 controls T cell metabolism and function: PIK3C3/VPS34 in T cell metabolism and function. Autophagy. 2021;17(5):1193–1204.
  • Araki K, Turner AP, Shaffer VO, et al. mTOR regulates memory CD8 T-cell differentiation. Nature. 2009;460(7251):108–112.
  • Uhl M, Kepp O, Jusforgues-Saklani H, et al. Autophagy within the antigen donor cell facilitates efficient antigen cross-priming of virus-specific CD8+ T cells. Cell Death & Differentiation. 2009;16(7):991–1005.
  • Wang Z, Han Q, Wang J, et al. Rapamycin induces autophagy and apoptosis in Kaposiform hemangioendothelioma primary cells in vitro. Journal of Pediatric Surgery. 2022;57(7):1274–1280.
  • Franciotta D, Salvetti M, Lolli F, et al. B cells and multiple sclerosis. The Lancet Neurology. 2008;7(9):852–858.
  • Wekerle H. B cells in multiple sclerosis. Autoimmunity. 2017;50(1):57–60.
  • Obermeier B, Mentele R, Malotka J, et al. Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis. Nature medicine. 2008;14(6):688–693.
  • Yu X, Graner M, Kennedy PG, et al. The role of antibodies in the pathogenesis of multiple sclerosis. Frontiers in neurology. 2020;11:533388.
  • Ikeda J, Shimojima Y, Yoshinaga T, et al. Alteration of BAFF and APRIL in the cerebrospinal fluid based on the therapeutic response in primary central nervous system B-cell lymphoma. Journal of Clinical Neuroscience. 2020;81:72–75.
  • Barun B, Bar-Or A. Treatment of multiple sclerosis with anti-CD20 antibodies. Clinical immunology. 2012;142(1):31–37.
  • Hauser SL, Waubant E, Arnold DL, et al. B-cell depletion with rituximab in relapsing–remitting multiple sclerosis. New England Journal of Medicine. 2008;358(7):676–688.
  • Gelfand JM, Cree BA, Hauser SL. Ocrelizumab and other CD20+ B-cell-depleting therapies in multiple sclerosis. Neurotherapeutics. 2017;14(4):835–841.
  • Mulero P, Midaglia L, Montalban X. Ocrelizumab: a new milestone in multiple sclerosis therapy. Therapeutic advances in neurological disorders. 2018;11:1756286418773025.
  • Sospedra M. B cells in multiple sclerosis. Current opinion in neurology. 2018;31(3):256–262.
  • Arneth BM. Impact of B cells to the pathophysiology of multiple sclerosis. Journal of Neuroinflammation. 2019;16:1–9.
  • Miller BC, Zhao Z, Stephenson LM, et al. The autophagy gene ATG5 plays an essential role in B lymphocyte development. Autophagy. 2008;4(3):309–314.
  • Sandoval H, Kodali S, Wang J. Regulation of B cell fate, survival, and function by mitochondria and autophagy. Mitochondrion. 2018;41:58–65.
  • Raza IG, Clarke AJ. B cell metabolism and autophagy in autoimmunity. Frontiers in Immunology. 2021;12:681105.
  • Zhang Y, Hu T, Hua C, et al. Rictor is required for early B cell development in bone marrow. PLoS One. 2014;9(8):e103970.
  • Clarke AJ, Riffelmacher T, Braas D, et al. B1a B cells require autophagy for metabolic homeostasis and self-renewal. Journal of Experimental Medicine. 2018;215(2):399–413.
  • Li R, Patterson KR, Bar-Or A. Reassessing B cell contributions in multiple sclerosis. Nature immunology. 2018;19(7):696–707.
  • Li R, Tang H, Burns JC, et al. BTK inhibition limits B-cell–T-cell interaction through modulation of B-cell metabolism: Implications for multiple sclerosis therapy. Acta Neuropathologica. 2022;143(4):505–521.
  • Fraussen J, Claes N, Van Wijmeersch B, et al. B cells of multiple sclerosis patients induce autoreactive proinflammatory T cell responses. Clinical Immunology. 2016;173:124–132.
  • Harp CT, Lovett-Racke AE, Racke MK, et al. Impact of myelin-specific antigen presenting B cells on T cell activation in multiple sclerosis. Clinical immunology. 2008;128(3):382–391.
  • Delfan N, Galehdari H, Mardasi FG, et al. Association of HLA-DR2-Related Haplotype (HLA-DRB5* 01-DRB1* 1501-DQB1* 0602) in Patients with Multiple Sclerosis in Khuzestan Province. Iranian Journal of Child Neurology. 2021;15(3):35.
  • DCunha A, Pandit L, Malli C, et al. Evaluating the role of HLA DRB1 alleles and oligoclonal bands in influencing clinical course of multiple sclerosis–A study from the Mangalore demyelinating disease registry. Annals of Indian Academy of Neurology. 2021;24(3):356.
  • Kantarci OH, de Andrade M, Weinshenker BG. Identifying disease modifying genes in multiple sclerosis. Journal of neuroimmunology. 2002;123(1–2):144–159.
  • Barcellos L, Oksenberg J, Begovich A, et al. HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course. The American Journal of Human Genetics. 2003;72(3):710–716.
  • Voet S, Prinz M, van Loo G. Microglia in central nervous system inflammation and multiple sclerosis pathology. Trends in molecular medicine. 2019;25(2):112–123.
  • Ye J, Jiang Z, Chen X, et al. The role of autophagy in pro‐inflammatory responses of microglia activation via mitochondrial reactive oxygen species in vitro. Journal of neurochemistry. 2017;142(2):215–230.
  • Shao BZ, Wei W, Ke P, et al. Activating cannabinoid receptor 2 alleviates pathogenesis of experimental autoimmune encephalomyelitis via activation of autophagy and inhibiting NLRP 3 inflammasome. CNS neuroscience & therapeutics. 2014;20(12):1021–1028.
  • Berglund R, Guerreiro-Cacais AO, Adzemovic MZ, et al. Microglial autophagy–associated phagocytosis is essential for recovery from neuroinflammation. Science immunology. 2020;5(52):eabb5077.
  • Skripuletz T, Hackstette D, Bauer K, et al. Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination. Brain. 2013;136(1):147–167.
  • Wang J-L, Xu C-J. Astrocytes autophagy in aging and neurodegenerative disorders. Biomedicine & Pharmacotherapy. 2020;122:109691.
  • Keller CW, Sina C, Kotur MB, et al. ATG-dependent phagocytosis in dendritic cells drives myelin-specific CD4+ T cell pathogenicity during CNS inflammation. Proceedings of the National Academy of Sciences. 2017;114(52):E11228–E11237.
  • Nuyts AH, Lee W, Bashir-Dar R, et al. Dendritic cells in multiple sclerosis: key players in the immunopathogenesis, key players for new cellular immunotherapies? Multiple Sclerosis Journal. 2013;19(8):995–1002.
  • Zhen C, Feng X, Li Z, et al. Suppression of murine experimental autoimmune encephalomyelitis development by 1, 25-dihydroxyvitamin D3 with autophagy modulation. Journal of neuroimmunology. 2015;280:1–7.
  • Harris J. Autophagy and cytokines. Cytokine. 2011;56(2):140–144.
  • Lapaquette P, Bringer MA, Darfeuille‐Michaud A. Defects in autophagy favour adherent‐invasive Escherichia coli persistence within macrophages leading to increased pro‐inflammatory response. Cellular microbiology. 2012;14(6):791–807.
  • Cui B, Lin H, Yu J, et al. Autophagy and the immune response. Autophagy: Biology and Diseases: Basic Science. 2019:595–634.
  • Lee JP, Foote A, Fan H, et al. Loss of autophagy enhances MIF/macrophage migration inhibitory factor release by macrophages. Autophagy. 2016;12(6):907–916.
  • Ashrafizadeh M, Ahmadi Z, Mohammadinejad R, et al. Monoterpenes modulating autophagy: A review study. Basic & Clinical Pharmacology & Toxicology. 2020;126(1):9–20.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.