Trehalose consumption ameliorates pathogenesis in an inducible mouse model of the Fragile X-associated tremor/ataxia syndrome

References

• Richards AB, Krakowka S, Dexter LB, Schmid H, Wolterbeek APM, Waalkens-Berendsen DH, et al. Trehalose: a review of properties, history of use and human tolerance, and results of multiple safety studies. Food Chem Toxicol. 2002;40(7):871–98.
   PubMed Web of Science ®Google Scholar
• Moriano ME, Alamprese C. Honey, trehalose and erythritol as sucrose-alternative sweeteners for artisanal ice cream. A pilot study. LWT. 2017;75:329–34.
   Web of Science ®Google Scholar
• Lee J, Lin E-W, Lau UY, Hedrick JL, Bat E, Maynard HD. Trehalose glycopolymers as excipients for protein stabilization. Biomacromolecules. 2013;14(8):2561–9.
   PubMed Web of Science ®Google Scholar
• Stefanello RF, Machado AAR, Pasqualin Cavalheiro C, Bartholomei Santos ML, Nabeshima EH, Copetti MV, Fries LLM. Trehalose as a cryoprotectant in freeze-dried wheat sourdough production. LWT. 2018;89:510–7.
   Web of Science ®Google Scholar
• Tanaka M, Machida Y, Niu S, Ikeda T, Jana NR, Doi H, et al. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat Med. 2004;10(2):148–54.
   PubMed Web of Science ®Google Scholar
• Li Y, Guo Y, Wang X, Yu X, Duan W, Hong K, et al. Trehalose decreases mutant SOD1 expression and alleviates motor deficiency in early but not end-stage amyotrophic lateral sclerosis in a SOD1-G93A mouse model. Neuroscience. 2015;298:12–25.
   PubMed Web of Science ®Google Scholar
• Santana MM, Paixão S, Cunha-Santos J, Silva TP, Trevino-Garcia A, Gaspar LS, et al. Trehalose alleviates the phenotype of Machado–Joseph disease mouse models. J Transl Med. 2020;18(1):161.
   PubMed Web of Science ®Google Scholar
• Sahdeo S, Tomilov A, Komachi K, Iwahashi C, Datta S, Hughes O, et al. High-throughput screening of FDA-approved drugs using oxygen biosensor plates reveals secondary mitofunctional effects. Mitochondrion. 2014;17:116–25.
   PubMed Web of Science ®Google Scholar
• Hagerman RJ, Hagerman P. Fragile X-associated tremor/ataxia syndrome—features, mechanisms and management. Nat Rev Neurol. 2016;12(7):403–12.
   PubMed Web of Science ®Google Scholar
• Reddy K, Cleary JD, Berglund JA. Drug screen tugs at common thread for repeat disorders. Trends Pharmacol Sci. 2020;41(2):71–73.
   PubMed Web of Science ®Google Scholar
• Higuchi Y, Ando M, Yoshimura A, Hakotani S, Koba Y, Sakiyama Y, et al. Prevalence of Fragile X-associated tremor/ataxia syndrome in patients with cerebellar ataxia in Japan. The Cerebellum. 2021;21(5):851–60.
   PubMed Web of Science ®Google Scholar
• Jacquemont S. Penetrance of the Fragile X–associated tremor/ataxia syndrome in a premutation carrier population. JAMA. 2004;291(4):460.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Revenga L, Madrigal I, Pagonabarraga J, Xunclà M, Badenas C, Kulisevsky J, et al. Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families. Eur J Hum Genet. 2009;17(10):1359–62.
   PubMed Web of Science ®Google Scholar
• Rousseau F, Heitz D, Biancalana V, Blumenfeld S, Kretz C, Boué J, et al. Direct diagnosis by DNA analysis of the Fragile X syndrome of mental retardation. N Engl J Med. 1991;325(24):1673–81.
   PubMed Web of Science ®Google Scholar
• Zhao X-N, Usdin K. Ups and downs: mechanisms of repeat instability in the Fragile X-related disorders. Genes (Basel). 2016;7(9):70.
   PubMed Web of Science ®Google Scholar
• Gohel D, Sripada L, Prajapati P, Singh K, Roy M, Kotadia D, et al. FMRpolyG alters mitochondrial transcripts level and respiratory chain complex assembly in Fragile X associated tremor/ataxia syndrome [FXTAS]. Biochim Biophys Acta BBA – Mol Basis Dis. 2019;1865(6):1379–88.
   PubMed Web of Science ®Google Scholar
• Hukema RK, Buijsen RAM, Schonewille M, Raske C, Severijnen L-AWFM, Nieuwenhuizen-Bakker I, et al. Reversibility of neuropathology and motor deficits in an inducible mouse model for FXTAS. Hum Mol Genet. 2015;24(17):4948–57.
   PubMed Web of Science ®Google Scholar
• Castro H, Kul E, Buijsen RAM, Severijnen L-AWFM, Willemsen R, Hukema RK, et al. Selective rescue of heightened anxiety but not gait ataxia in a premutation 90CGG mouse model of Fragile X-associated tremor/ataxia syndrome. Hum Mol Genet. 2017;26(11):2133–45.
   PubMed Web of Science ®Google Scholar
• Derbis M, Kul E, Niewiadomska D, Sekrecki M, Piasecka A, Taylor K, et al. Short antisense oligonucleotides alleviate the pleiotropic toxicity of RNA harboring expanded CGG repeats. Nat Commun. 2021;12(1):1265.
   PubMed Web of Science ®Google Scholar
• Mardones P, Rubinsztein DC, Hetz C. Mystery solved: trehalose kickstarts autophagy by blocking glucose transport. Sci Signal. 2016;9:416.
   Web of Science ®Google Scholar
• Tanida I, Waguri S. Measurement of Autophagy in Cells and Tissues. In: Bross P, Gregersen N, editor. Protein misfolding cell stress dis aging. Vol. 648. Totowa, NJ: Humana Press; 2010. p. 193–214.
   Google Scholar
• Howson PA, Johnston TH, Ravenscroft P, Hill MP, Su J, Brotchie JM, Koprich JB. Beneficial effects of trehalose on striatal dopaminergic deficits in rodent and primate models of synucleinopathy in Parkinson’s disease. J Pharmacol Exp Ther. 2019;369(3):364–74.
   PubMed Web of Science ®Google Scholar
• Gao Z, Wang H, Zhang B, Wu X, Zhang Y, Ge P, et al. Trehalose inhibits H2O2-induced autophagic death in dopaminergic SH-SY5Y cells via mitigation of ROS-dependent endoplasmic reticulum stress and AMPK activation. Int J Med Sci. 2018;15(10):1014–24.
   PubMed Web of Science ®Google Scholar
• Mizunoe Y, Kobayashi M, Sudo Y, Watanabe S, Yasukawa H, Natori D, et al. Trehalose protects against oxidative stress by regulating the Keap1–Nrf2 and autophagy pathways. Redox Biol. 2018;15:115–24.
   PubMed Web of Science ®Google Scholar
• Buckley AM, Moura IB, Arai N, Spittal W, Clark E, Nishida Y, et al. Trehalose-induced remodelling of the human microbiota affects clostridioides difficile infection outcome in an in vitro colonic model: a pilot study. Front Cell Infect Microbiol. 2021;11:670935.
   PubMed Web of Science ®Google Scholar
• Tanji K, Miki Y, Maruyama A, Mimura J, Matsumiya T, Mori F, et al. Trehalose intake induces chaperone molecules along with autophagy in a mouse model of Lewy body disease. Biochem Biophys Res Commun. 2015;465(4):746–52.
   PubMed Web of Science ®Google Scholar
• Lee H-J, Yoon Y-S, Lee S-J. Mechanism of neuroprotection by trehalose: controversy surrounding autophagy induction. Cell Death Dis. 2018;9(7):712.
   PubMedGoogle Scholar
• Ma L, Herren AW, Espinal G, Randol J, McLaughlin B, Martinez-Cerdeño V, et al. Composition of the intranuclear inclusions of Fragile X-associated tremor/ataxia syndrome. Acta Neuropathol Commun. 2019;7(1):143.
   PubMed Web of Science ®Google Scholar
• Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016;12(1):1–222.
   PubMed Web of Science ®Google Scholar
• Pankiv S, Clausen TH, Lamark T, Brech A, Bruun J-A, Outzen H, et al. p62/SQSTM1 Binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem. 2007;282(33):24131–45.
   PubMed Web of Science ®Google Scholar
• Sergin I, Evans TD, Zhang X, Bhattacharya S, Stokes CJ, Song E, et al. Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis. Nat Commun. 2017;8:15750.
   PubMed Web of Science ®Google Scholar
• Garcia-Arocena D, Yang JE, Brouwer JR, Tassone F, Iwahashi C, Berry-Kravis EM, et al. Fibroblast phenotype in male carriers of FMR1 premutation alleles. Hum Mol Genet. 2010;19(2):299–312.
   PubMed Web of Science ®Google Scholar
• Vornovitzki H, Blotnick S, Gliko-Kabir I, Argov Z, Caraco Y. Characterization of blood glucose & glycosuria following IV trehalose (Cabaletta) administration for OPMD. Clin Ther. 2015;37(8):e80.
   Web of Science ®Google Scholar
• Argov Z, Gliko-Kabir I, Brais B, Caraco Y, Megiddo D. Intravenous trehalose improves dysphagia and muscle function in oculopharyngeal muscular dystrophy (OPMD): preliminary results of 24 weeks open label phase 2 Trial (S28.004). Neurology. 2016;86(16 Supplement.
   Google Scholar
• Foote M, Arque G, Berman RF, Santos M. Fragile X-associated tremor/ataxia syndrome (FXTAS) motor dysfunction modeled in mice. The Cerebellum. 2016;15(5):611–22.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Shaikh N, Ferey JL, Wankhade UD, Chintapalli SV, Higgins CB, et al. Lactotrehalose, an analog of trehalose, increases energy metabolism without promoting clostridioides difficile infection in mice. Gastroenterology. 2020;158(5):1402–16. e2.
   PubMed Web of Science ®Google Scholar
• Noorasyikin MA, Azizan EA, Teh PC, Farah Waheeda T, Siti Hajar MD, Long KC, Norlinah MI. Oral trehalose maybe helpful for patients with spinocerebellar ataxia 3 and should be better evaluated. Parkinsonism Relat Disord. 2020;70:42–44.
   PubMed Web of Science ®Google Scholar
• O’Keefe JA, Bang D, Robertson EE, Biskis A, Ouyang B, Liu Y, et al. Prodromal markers of upper limb deficits in FMR1 premutation carriers and quantitative outcome measures for future clinical trials in Fragile X-associated tremor/ataxia syndrome. Mov Disord Clin Pract. 2020;7(7):810–9.
   PubMed Web of Science ®Google Scholar