Ibrutinib Delays ALS Installation and Increases Survival of SOD1G93A Mice by Modulating PI3K/mTOR/Akt Signaling

Aalipour A, Advani RH (2014) Bruton’s tyrosine kinase inhibitors and their clinical potential in the treatment of B-cell malignancies: focus on ibrutinib. Ther Adv Hematol 5(4):121–133. https://doi.org/10.1177/2040620714539906

Article  CAS  PubMed  PubMed Central  Google Scholar 

Barrientos J, Rai K (2013) Ibrutinib: a novel Bruton’s tyrosine kinase inhibitor with outstanding responses in patients with chronic lymphocytic leukemia. Leuk Lymphoma 54(8):1817–1820. https://doi.org/10.3109/10428194.2013.796049

Article  CAS  PubMed  Google Scholar 

Bendotti C, Carrì MT (2004) Lessons from models of SOD1-linked familial ALS. Trends Mol Med 10(8):393–400. https://doi.org/10.1016/j.molmed.2004.06.009

Article  CAS  PubMed  Google Scholar 

Calvo A, Moglia C, Balma M, Chio A (2010) Involvement of immune response in the pathogenesis of amyotrophic lateral sclerosis: a therapeutic opportunity? CNS & neurological Disorders-Drug targets (formerly current drug Targets-CNS &amp. Neurol Disorders) 9(3):325–330

CAS  Google Scholar 

Comley LH, Nijssen J, Frost-Nylen J, Hedlund E (2016) Cross-disease comparison of amyotrophic lateral sclerosis and spinal muscular atrophy reveals conservation of selective vulnerability but differential neuromuscular junction pathology. J Comp Neurol 524(7):1424–1442. https://doi.org/10.1002/cne.23917

Article  PubMed  Google Scholar 

de Porto AP, Liu Z, de Beer R, Florquin S, de Boer OJ, Hendriks RW, de Vos AF (2019) Btk inhibitor ibrutinib reduces inflammatory myeloid cell responses in the lung during murine pneumococcal pneumonia. Mol Med 25(1):3. https://doi.org/10.1186/s10020-018-0069-7

Article  PubMed  PubMed Central  Google Scholar 

Dewil M, Lambrechts D, Sciot R, Shaw PJ, Ince PG, Robberecht W, Van den Bosch L (2007) Vascular endothelial growth factor counteracts the loss of phospho-akt preceding motor neurone degeneration in amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol 33(5):499–509. https://doi.org/10.1111/j.1365-2990.2007.00850.x

Article  CAS  PubMed  Google Scholar 

Dobrowolny G, Aucello M, Rizzuto E, Beccafico S, Mammucari C, Boncompagni S, Musarò A (2008) Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. Cell Metab 8(5):425–436. https://doi.org/10.1016/j.cmet.2008.09.002

Article  PubMed  Google Scholar 

Frakes AE, Ferraiuolo L, Haidet-Phillips AM, Schmelzer L, Braun L, Miranda CJ, Godbout JP (2014) Microglia induce motor neuron death via the classical NF-κB pathway in amyotrophic lateral sclerosis. Neuron 81(5):1009–1023

Article  CAS  PubMed  PubMed Central  Google Scholar 

Goldwirt L, Beccaria K, Ple A, Sauvageon H, Mourah S (2018) Ibrutinib brain distribution: a preclinical study. Cancer Chemother Pharmacol 81(4):783–789. https://doi.org/10.1007/s00280-018-3546-3

Article  CAS  PubMed  Google Scholar 

Gonzalez D, Rebolledo DL, Correa LM, Court FA, Cerpa W, Lipson KE, Brandan E (2018) The inhibition of CTGF/CCN2 activity improves muscle and locomotor function in a murine ALS model. Hum Mol Genet 27(16):2913–2926. https://doi.org/10.1093/hmg/ddy204

Article  CAS  PubMed  Google Scholar 

Granatiero V, Sayles NM, Savino AM, Konrad C, Kharas MG, Kawamata H, Manfredi G (2021) Modulation of the IGF1R-MTOR pathway attenuates motor neuron toxicity of human ALS SOD1(G93A) astrocytes. Autophagy 17(12):4029–4042. https://doi.org/10.1080/15548627.2021.1899682

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gros-Louis F, Gaspar C, Rouleau GA (2006) Genetics of familial and sporadic amyotrophic lateral sclerosis. Biochim Biophys Acta 1762(11–12):956–972. https://doi.org/10.1016/j.bbadis.2006.01.004

Article  CAS  PubMed  Google Scholar 

Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD et al (1994) Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264(5166):1772–1775. https://doi.org/10.1126/science.8209258

Article  CAS  PubMed  Google Scholar 

He L, Pei H, Zhang C, Shao M, Li D, Tang M, Chen L (2018) Design, synthesis and biological evaluation of 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as selective Btk inhibitors with improved pharmacokinetic properties for the treatment of rheumatoid arthritis. Eur J Med Chem 145:96–112. https://doi.org/10.1016/j.ejmech.2017.12.079

Article  CAS  PubMed  Google Scholar 

Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J, Pedraza-Chaverri J (2014) The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal 26(12):2694–2701. https://doi.org/10.1016/j.cellsig.2014.08.019

Article  CAS  PubMed  Google Scholar 

Hooten KG, Beers DR, Zhao W, Appel SH (2015) Protective and toxic neuroinflammation in amyotrophic lateral sclerosis. Neurotherapeutics 12(2):364–375. https://doi.org/10.1007/s13311-014-0329-3

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hu Y, Cao C, Qin X-Y, Yu Y, Yuan J, Zhao Y, Cheng Y (2017) Increased peripheral blood inflammatory cytokine levels in amyotrophic lateral sclerosis: a meta-analysis study. Sci Rep 7(1):9094. https://doi.org/10.1038/s41598-017-09097-1

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kuwabara S, Sonoo M, Komori T, Shimizu T, Hirashima F, Inaba A, Hatanaka Y (2008) Dissociated small hand muscle atrophy in amyotrophic lateral sclerosis: frequency, extent, and specificity. Muscle Nerve 37(4):426–430. https://doi.org/10.1002/mus.20949

Article  PubMed  Google Scholar 

Lenglet T, Camdessanché JP (2017) Amyotrophic lateral sclerosis or not: Keys for the diagnosis. Rev Neurol (Paris) 173(5):280–287. https://doi.org/10.1016/j.neurol.2017.04.003

Article  CAS  PubMed  Google Scholar 

Li Q, Vande Velde C, Israelson A, Xie J, Bailey AO, Dong MQ, Miller TM (2010) ALS-linked mutant superoxide dismutase 1 (SOD1) alters mitochondrial protein composition and decreases protein import. Proc Natl Acad Sci U S A 107(49):21146–21151. https://doi.org/10.1073/pnas.1014862107

Article  PubMed  PubMed Central  Google Scholar 

Li B, Xi P, Wang Z, Han X, Xu Y, Zhang Y, Miao J (2018) PI3K/Akt/mTOR signaling pathway participates in Streptococcus uberis-induced inflammation in mammary epithelial cells in concert with the classical TLRs/NF-ĸB pathway. Vet Microbiol 227:103–111. https://doi.org/10.1016/j.vetmic.2018.10.031

Article  CAS  PubMed  Google Scholar 

Liu J, Wang F (2017) Role of Neuroinflammation in Amyotrophic lateral sclerosis: Cellular Mechanisms and therapeutic implications. Front Immunol 8:1005. https://doi.org/10.3389/fimmu.2017.01005

Article  CAS  PubMed  PubMed Central  Google Scholar 

Logroscino G, Traynor BJ, Hardiman O, Chiò A, Mitchell D, Swingler RJ, Beghi E (2010) Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry 81(4):385–390. https://doi.org/10.1136/jnnp.2009.183525

Article  PubMed  Google Scholar 

Longinetti E, Fang F (2019) Epidemiology of amyotrophic lateral sclerosis: an update of recent literature. Curr Opin Neurol 32(5):771–776. https://doi.org/10.1097/wco.0000000000000730

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lyon MS, Wosiski-Kuhn M, Gillespie R, Caress J, Milligan C (2019) Inflammation, immunity, and amyotrophic lateral sclerosis: I. etiology and pathology. Muscle Nerve 59(1):10–22. https://doi.org/10.1002/mus.26289

Article  PubMed  Google Scholar 

Mandrioli J, D’Amico R, Zucchi E, Gessani A, Fini N, Fasano A, Cossarizza A (2018) Rapamycin treatment for amyotrophic lateral sclerosis: protocol for a phase II randomized, doubleblind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial). Med (Baltim) 97(24):e11119. https://doi.org/10.1097/md.0000000000011119

Mason C, Savona S, Rini JN, Castillo JJ, Xu L, Hunter ZR, Allen SL (2017) Ibrutinib penetrates the blood brain barrier and shows efficacy in the therapy of Bing Neel syndrome. Br J Haematol 179(2):339–341. https://doi.org/10.1111/bjh.14218

Article  CAS  PubMed  Google Scholar 

Menon P, Kiernan MC, Yiannikas C, Stroud J, Vucic S (2013) Split-hand index for the diagnosis of amyotrophic lateral sclerosis. Clin Neurophysiol 124(2):410–416. https://doi.org/10.1016/j.clinph.2012.07.025

Article  PubMed  Google Scholar 

Min YG, Choi S-J, Hong Y-H, Kim S-M, Shin J-Y, Sung J-J (2020) Dissociated leg muscle atrophy in amyotrophic lateral sclerosis/motor neuron disease: the ‘split-leg’ sign. Sci Rep 10(1):15661. https://doi.org/10.1038/s41598-020-72887-7

Article  CAS  PubMed  PubMed Central  Google Scholar 

Murdock BJ, Bender DE, Segal BM, Feldman EL (2015) The dual roles of immunity in ALS: injury overrides protection. Neurobiol Dis 77:1–12

Article  CAS  PubMed  Google Scholar 

Nam HY, Nam JH, Yoon G, Lee JY, Nam Y, Kang HJ, Hoe HS (2018) Ibrutinib suppresses LPS-induced neuroinflammatory responses in BV2 microglial cells and wild-type mice. J Neuroinflammation 15(1):271. https://doi.org/10.1186/s12974-018-1308-0

Article  CAS  PubMed  PubMed Central  Google Scholar 

Namikawa K, Honma M, Abe K, Takeda M, Mansur K, Obata T, Kiyama H (2000) Akt/protein kinase B prevents injury-induced motoneuron death and accelerates axonal regeneration. J Neurosci 20(8):2875–2886. https://doi.org/10.1523/jneurosci.20-08-02875.2000

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pansarasa O, Bordoni M, Diamanti L, Sproviero D, Gagliardi S, Cereda C (2018) SOD1 in amyotrophic lateral sclerosis: “Ambivalent” behavior connected to the Disease. Int J Mol Sci 19(5). https://doi.org/10.3390/ijms19051345

Pasinelli P, Brown RH (2006) Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat Rev Neurosci 7(9):710–723. https://doi.org/10.1038/nrn1971

Article  CAS  PubMed 

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