Skip to main content

Fungal Neurotoxins and Sporadic Amyotrophic Lateral Sclerosis

Abstract

We review several lines of evidence that point to a potential fungal origin of sporadic amyotrophic lateral sclerosis (ALS). ALS is the most common form of motor neuron disease (MND) in adults. It is a progressive and fatal disease. Approximately 90% cases of ALS are sporadic, and 5–10% are due to genetic mutations (familial). About 25 genes implicated in familial ALS have been identified so far, including SOD1 and TARDBP, the gene encoding 43 kDa transactive response (TAR) DNA-binding protein (TDP-43). Despite intensive research over many decades, the aetiology of sporadic ALS is still unknown. An environmental cause, including grass or soil-associated fungal infections, is suggested from a range of widely diverse lines of evidence. Clusters of ALS have been reported in soccer players, natives of Guam and farmers. Grass-associated fungi are known to produce a range of neurotoxins and, in symbiotic associations, high levels of fungal SOD1. Exposure of neurons to fungal neurotoxins elicits a significant increase in glutamate production. High levels of glutamate stimulate TDP-43 translocation and modification, providing a link between fungal infection and one of the molecular and histologic hallmarks of sporadic ALS. A recent study provided evidence of a variety of fungi in the cerebrospinal fluid and brain tissue of ALS patients. This review provides a rational explanation for this observation. If a fungal infection could be confirmed as a potential cause of ALS, this could provide a straightforward treatment strategy for this fatal and incurable disease.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

Notes

  1. http://www.pacsoa.org.au/palms/Articles/pests2.html

References

  • Al-Chalabi A, Jones A, Troakes C, King A, Al-Sarraj S et al (2012) The genetics and neuropathology of amyotrophic lateral sclerosis. Acta Neuropathol 124:339–352

    Article  CAS  PubMed  Google Scholar 

  • Alfahad T, Nath A (2013) Retroviruses and amyotrophic lateral sclerosis. Antivir Res 99(2):180–187

    Article  CAS  PubMed  Google Scholar 

  • Alonso R, Pisa D, Fernández-Fernández AM, Rábano A, Carrasco L (2017) Fungal infection in neural tissue of patients with amyotrophic lateral sclerosis. Neurobiol Dis 108:249–260

    Article  CAS  PubMed  Google Scholar 

  • Alonso R, Pisa D, Marina AI, Morato E, Rábano A, Rodal I, Carrasco L (2015) Evidence for fungal infection in cerebrospinal fluid and brain tissue from patients with amyotrophic lateral sclerosis. Int J Biol Sci 11:546–558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alshannaq A, Yu J-H (2017) Occurrence, toxicity, and analysis of major mycotoxins in food. Int J Environ Res Public Health 4(6):632–652

    Article  CAS  Google Scholar 

  • Andersen PM, Al-Chalabi A (2011) Clinical genetics of amyotrophic lateral sclerosis: what do we really know? Nat Rev Neurol 7:603–615

    Article  CAS  PubMed  Google Scholar 

  • Bassini A, Cameron LC (2014) Sportomics: building a new concept in metabolic studies and exercise science. Biochem Biophys Res Commun 445:708–716

    Article  CAS  PubMed  Google Scholar 

  • Bhandari R, Kuhad A, Kuhad A (2018) Edaravone: a new hope for deadly amyotrophic lateral sclerosis. Drugs Today (Barc) 54(6):349–360

    Article  CAS  Google Scholar 

  • Bozzoni V, Pansarasa O, Diamanti L, Nosari G, Cereda C et al (2016) Amyotrophic lateral sclerosis and environmental factors. Funct Neurol 31(1):7–19

    PubMed  PubMed Central  Google Scholar 

  • Bradford HF, Norris PJ, Smith CC (1990) Changes in transmitter release patterns in vitro induced by tremorgenic mycotoxins. J Environ Pathol Toxicol Oncol 10(1–2):17–30

    CAS  PubMed  Google Scholar 

  • Bradley WG, Stommel EW, Shi X, Torbick NM, Caller TA et al (2015) Spatial cluster analysis of population amyotrophic lateral sclerosis risk in Ireland. Neurology 85(20):1822–1823

    Article  PubMed  Google Scholar 

  • Carroll MC, Girouard JB, Ulloa JL, Subramaniam JR, Wong PC, Valentine JS, Culotta VC (2004) Mechanisms for activating Cu- and Zn-containing superoxide dismutase in the absence of the CCS Cu chaperone. Proc Natl Acad Sci U S A 101:5964–5969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Castanedo-Vazquez D, Bosque-Varela P, Sainz-Pelayo A, Riancho J (2018) Infectious agents and amyotrophic lateral sclerosis: another piece of the puzzle of motor neuron degeneration. J Neurol. https://doi.org/10.1007/s00415-018-8919-3

  • Cellura E (2011) Extramotor disorders in amyotrophic lateral sclerosis: multisystem disease? Clin Ter 162:457–459

    CAS  PubMed  Google Scholar 

  • Cheah BC, Vucic S, Krishnan AV, Kiernan MC (2010) Riluzole, neuroprotection and amyotrophic lateral sclerosis. Curr Med Chem 17:1942–1959

    Article  CAS  PubMed  Google Scholar 

  • Chiò A, Benzi G, Dossena M, Mutani R, Mora G (2005) Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players. Brain 128:472–476

    Article  PubMed  Google Scholar 

  • Chiò A, Calvo A, Dossena M, Ghiglione P, Mutani R, Mora G (2009) ALS in Italian professional soccer players: the risk is still present and could be soccer-specific. Amyotroph Lateral Scler 10:205–209

    Article  PubMed  Google Scholar 

  • Chió A, Meineri P, Tribolo A, Schiffer D (1991) Risk factors in motor neuron disease: a case-control study. Neuroepidemiol 10:174–184

    Article  Google Scholar 

  • Cole RJ (1981) Fungal tremorgens. J Food Protection 44:715–722

    Article  CAS  Google Scholar 

  • Cox GM, Harrison TS, McDade HC, Taborda CP, Heinrich G et al (2003b) Superoxide dismutase influences the virulence of Cryptococcus neoformans by affecting growth within macrophages. Infect Immun 71(1):173–180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox PA, Banack SA, Murch SJ (2003a) Biomagnification of cyanobacterial neurotoxins and neurodegenerative disease among the Chamorro people of Guam. Natl Acad Sci USA 100(23):13380–13383

    Article  CAS  Google Scholar 

  • Cox PA, Kostrzewa RM, Guillemin GJ (2018) BMAA and neurodegenerative illness. Neurotox Res 33(1):178–183

    Article  PubMed  Google Scholar 

  • di Menna ME, Finch SC, Popay J, Smith BL (2012) A review of the Neotyphodium lolii / Lolium perenne symbiosis and its associated effects on animal and plant health, with particular emphasis on ryegrass staggers. NZ Vet J 60(6):315–328

    Article  Google Scholar 

  • Doble A (1996) The pharmacology and mechanism of action of riluzole. Neurology 47(6 Suppl 4):S233–S241

    Article  CAS  PubMed  Google Scholar 

  • Douville R, Liu J, Rothstein J, Nath A (2011) Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis. Ann Neurol 69(1):141–151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dupuis L, Pradat PF, Ludolph AC, Loeffler JP (2011) Energy metabolism in amyotrophic lateral sclerosis. Lancet Neurol 10:75–82

    Article  CAS  PubMed  Google Scholar 

  • el Khoury A, Atoui A (2010) Ochratoxin A: general overview and actual molecular status. Toxins 2:461–493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang F, Hallmarker U, James S, Ingre C, Michaelsson K et al (2015) Amyotrophic lateral sclerosis among cross-country skiers in Sweden. Eur J Epidemiol 31:247–253. https://doi.org/10.1007/s10654-015-0077-7

    Article  PubMed  Google Scholar 

  • Furby A, Beauvais K, Kolev I, Rivain JG, Sébille V (2010) Rural environment and risk factors of amyotrophic lateral sclerosis: a case-control study. J Neurol 257:792–798

    Article  PubMed  Google Scholar 

  • Gallagher RT, Keogh RG, Latch GCM, Reid CSW (1977) The role of fungal tremorgens in ryegrass staggers. NZ J Agr 20:431–440

    Article  Google Scholar 

  • Gallo V, Vanacore N, Bueno-de-Mesquita HB (2016) Physical activity and risk of amyotrophic lateral sclerosis in a prospective cohort study. Eur J Epidemiol 31(3):255–266

    Article  PubMed  PubMed Central  Google Scholar 

  • Gitler AD, Tsuiji H (2016) There has been an awakening: emerging mechanisms of C9orf72 mutations in FTD/ALS. Brain Res 1647:19–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gordon PH (2013) Amyotrophic lateral sclerosis: an update for 2013 clinical features, pathophysiology, management and therapeutic trials. Aging Dis 4:295–310

    Article  PubMed  PubMed Central  Google Scholar 

  • Haley RW (2003) Excess incidence of ALS in young Gulf War veterans. Neurology 61(6):750–756

    Article  PubMed  Google Scholar 

  • Haque AK (1992) Pathology of common pulmonary fungal infections. J Thorac Imaging 7(4):1–11

    Article  CAS  PubMed  Google Scholar 

  • Hochberg FH, Bryan JA 2nd, Whelan MA (1974) Clustering of amyotrophic lateral sclerosis. Lancet 1(7845):34

    Article  CAS  PubMed  Google Scholar 

  • Howard R, Orrell R (2002) Management of motor neurone disease. Postgrad Med J 78(926):736–741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ince PG, Codd GA (2005) Return of the cycad hypothesis—does the amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) of Guam have new implications for global health? Neuropathol Appl Neurobiol 31(4):345–353

    Article  CAS  PubMed  Google Scholar 

  • Ingre C, Roos PM, Piehl F, Kamel F, Fang F (2015) Risk factors for amyotrophic lateral sclerosis. Clin Epidemiol 7:181–193

    PubMed  PubMed Central  Google Scholar 

  • Kang H, Cha ES, Choi GJ, Lee WJ (2014) Amyotrophic lateral sclerosis and agricultural environments: a systematic review. J Korean Med Sci 29:1610–1617

    Article  PubMed  PubMed Central  Google Scholar 

  • Kilness AW, Hochberg FH (1977) Amyotrophic lateral sclerosis in a high selenium environment. JAMA 237(26):2843–2844

    Article  CAS  PubMed  Google Scholar 

  • King OD, Gitler AD, Shorter J (2012) The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. Brain Res 1462:61–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kisby GE, Spencer PS (2011) Is neurodegenerative disease a long-latency response to early-life genotoxin exposure? Int J Environ Res Public Health 8(10):3889–3921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kurland LT (1988) Amyotrophic lateral sclerosis and Parkinson’s disease complex on Guam linked to an environmental neurotoxin. Trends Neurosci 11:51–54

    Article  CAS  PubMed  Google Scholar 

  • LaFleur MD, Lucumi E, Napper AD, Diamond SL, Lewis K (2011) Novel high-throughput screen against Candida albicans identifies antifungal potentiators and agents effective against biofilms. J Antimicrob Chemother 66:820–826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lahiani A, Yavin E, Lazarovici P (2017) The molecular basis of toxins’ interactions with intracellular signaling via discrete portals. Toxins 9:107–165

    Article  CAS  PubMed Central  Google Scholar 

  • Lasiene J, Yamanaka K (2011) Glial cells in amyotrophic lateral sclerosis. Neurol Res Int 2011:1–7. https://doi.org/10.1155/2011/718987

    Article  Google Scholar 

  • Mackenzie IRA, Rademakers R (2008) The role of TDP-43 in amyotrophic lateral sclerosis and frontotemporal dementia. Curr Opin Neurol 21(6):693–700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malaspina A, Alimonti D, Poloni TE, Ceroni M (2002) Disease clustering: the example of ALS, PD, dementia and hereditary ataxias in Italy. Funct Neurol 17(4):177–182

    PubMed  Google Scholar 

  • Mantle PG, Mortimer PH, White EP (1977) Mycotoxic tremorgens of Claviceps pascali and Penicillium cyclopium: a comparative study of effects of sheep and cattle in relation to natural staggers syndromes. Res Vet Sci 24:49–56

    Article  Google Scholar 

  • Masseret E, Banack S, Boumédiène F, Abadie E, Brient L, Pernet F, Juntas-Morales R, Pageot N, Metcalf J, Cox P, Camu W, Guillemin GJ (2013) Dietary BMAA Exposure in an Amyotrophic Lateral Sclerosis Cluster from Southern France. PLoS ONE 8(12):e83406. https://doi.org/10.1371/journal.pone.0083406

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Mathis S, Couratier P, Julian A, Corcia P, Le Masson G (2017) Current view and perspectives in amyotrophic lateral sclerosis. Neural Regen Res 12(2):181–184

    Article  PubMed  PubMed Central  Google Scholar 

  • Melmed C, Krieger C (1982) A cluster of amyotrophic lateral sclerosis. Arch Neurol 39(9):595–596

    Article  CAS  PubMed  Google Scholar 

  • Mochizuki Y, Isozaki E, Takao M, Hashimoto T, Shibuya M, Arai M, Hosokawa M, Kawata A, Oyanagi K, Mihara B, Mizutani T (2012) Familial ALS with FUS P525L mutation: two Japanese sisters with multiple systems involvement. J Neurol Sci 323:85–92

    Article  CAS  PubMed  Google Scholar 

  • Neumann M, Sampathu DM, Kwong LK, Trojanowski JQ, Lee VM (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314(5796):130–133

    Article  CAS  PubMed  Google Scholar 

  • Nicoletti A, Bruno E, Nania M, Cicero E, Messina S, Chisari C, Torrisi J, Maimone D, Marziolo R, Lo Fermo S, Patti F, Giammanco S, Zappia M (2013) Multiple sclerosis in the Mount Etna region: possible role of volcanogenic trace elements. PLoS One 8(12):e74259. https://doi.org/10.1371/journal.pone.0074259

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Nicoletti A, Vasta R, Venti V, Mostile G, Lo Fermo S, Patti F, Scillieri R, de Cicco D, Volanti P, Marziolo R, Maimone D, Fiore M, Ferrante M, Zappia M (2016) The epidemiology of amyotrophic lateral sclerosis in the Mount Etna region: a possible pathogenic role of volcanogenic metals. Eur J Neurol 23(5):964–972

    Article  CAS  PubMed  Google Scholar 

  • Norris PJ, Smith CCT, De Belleroche J, Bradford HF, Mantle PG et al (1980) Actions of tremorgenic fungal toxins on neurotransmitter release. J Neurochem 34(1):33–42

    Article  CAS  PubMed  Google Scholar 

  • Oskarsson B, Horton DK, Mitsumoto H (2015) Potential environmental factors in amyotrophic lateral sclerosis. Neurol Clin 33(4):877–888

    Article  PubMed  PubMed Central  Google Scholar 

  • Passler T, Walz PH, Pugh DG (2012) Diseases of the neurologic system. In Pugh DG, Baird AN (eds) Sheep and goat medicine, 2nd edn. Saunders, Maryland Heights, MO, pp 361–405

  • Peterson DW, Bradford HF, Mantle PG (1982a) Actions of a tremorgenic mycotoxin on amino acid transmitter release in vivo. Biochem Pharmacol 31:2807–2810

    Article  CAS  PubMed  Google Scholar 

  • Peterson DW, Penny RHC, Day JB, Mantle PG (1982b) A comparative study of sheep and pigs given the tremorgenic mycotoxins verruculogen and Penitrem A. Res Vet Sci 33(2):183–187

    Article  CAS  PubMed  Google Scholar 

  • Plumlee KH, Galey FD (1994) Neurotoxic mycotoxins: a review of fungal toxins that cause neurological disease in large animals. J Vet Intern Med 8:49–54

    Article  CAS  PubMed  Google Scholar 

  • Pokrishevsky E, Grad LI, Cashman NR (2016) TDP-43 or FUS-induced misfolded human wild-type SOD1 can propagate intercellularly in a prion-like fashion. Sci Rep 6:22155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ravits JM, La Spada AR (2009) Deconstructing motor neuron degeneration. Neurology 73(10):805–811

    Article  PubMed  PubMed Central  Google Scholar 

  • Riancho J, Bosque-Varela P, Perez-Pereda S, Povedano M, de Munaín AL, Santurtun A (2018) The increasing importance of environmental conditions in amyotrophic lateral sclerosis. Int J Biometeorol 62(8):1361–1374

    Article  PubMed  Google Scholar 

  • Renton AE, Majounie E, Waite A, Simón-Sánchez J, Rollinson S et al (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-Linked ALS-FTD. Neuron 72:257–268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rooney J, Heverin M, Vajda A, Elamin M, Crampsie A et al (2015) Spatial cluster analysis of population amyotrophic lateral sclerosis risk in Ireland. Neurology 84:1537–1544

    Article  PubMed  Google Scholar 

  • Rosati G, Pinna L, Granieri E, Aiello I, Tola R, Agnetti V, Pirisi A, Bastiani P (1977) Studies on epidemiological, clinical and etiological aspects of ALS disease in Sardinia, Southern Italy. Acta Neurol Scand 55(3):231–244

    Article  CAS  PubMed  Google Scholar 

  • Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O’Regan JP, Deng HX, Rahmani Z, Krizus A, McKenna-Yasek D, Cayabyab A, Gaston SM, Berger R, Tanzi RE, Halperin JJ, Herzfeldt B, van den Bergh R, Hung WY, Bird T, Deng G, Mulder DW, Smyth C, Laing NG, Soriano E, Pericak–Vance MA, Haines J, Rouleau GA, Gusella JS, Horvitz HR, Brown RH (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362(6415):59–62

    Article  CAS  PubMed  Google Scholar 

  • Roy J, Minotti S, Dong L, Figlewicz DA, Durham HD (1998) Glutamate potentiates the toxicity of mutant Cu/Zn-superoxide dismutase in motor neurons by postsynaptic calcium-dependent mechanisms. J Neurosci 18:9673–9684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sabel CE, Boyle PJ, Löytönen M, Gatrell AC, Jokelainen M et al (2003) Spatial clustering of amyotrophic lateral sclerosis in Finland at place of birth and place of death. Am J Epidemiol 157(10):898–905

    Article  CAS  PubMed  Google Scholar 

  • Sava V, Reunova O, Velasquez A, Sanchez-Ramos J (2006) Can low level exposure to ochratoxin-A cause parkinsonism? J Neurol Sci 249(1):68–75

    Article  CAS  PubMed  Google Scholar 

  • Scofield M, Korutla L, Jackson TG, Kalivas PW, Mackler SA (2012) Nucleus Accumbens 1, a Pox virus and Zinc finger/Bric-a-brac Tramtrack Broad protein binds to TAR DNA-binding protein 43 and has a potential role in amyotrophic lateral sclerosis. Neurosci 227:44–54

    Article  CAS  Google Scholar 

  • Selala MI, Daelemans F, Schepens PJ (1989) Fungal tremorgens: the mechanism of action of single nitrogen containing toxins—a hypothesis. Drug Chem Toxicol 12(3–4):237–257

    Article  CAS  PubMed  Google Scholar 

  • Sheng Y, Chattopadhyay M, Whitelegge J, Valentine JS (2012) SOD1 aggregation and ALS: role of metallation states and disulfide status. Curr Top Med Chem 12(22):2560–2572

    Article  CAS  PubMed  Google Scholar 

  • Sobotka TJ, Brodie RE, Spaid SL (1978) Neurobehavioral studies of tremorgenic mycotoxins verruculogen and penitrem A. Pharmacol 16(5):287–294

    Article  CAS  Google Scholar 

  • Spencer PS (1987) Guam ALS/parkinsonism-dementia: a long-latency neurotoxic disorder caused by “slow toxin(s)” in food? Canad J Neurol Sci 14(S3):347–357

    Article  CAS  PubMed  Google Scholar 

  • Steele JC (2005) Parkinsonism-dementia complex of Guam. Mov Disord 20(Suppl 12):S99–S107

  • Steele JC, McGeer PL (2008) The ALS/PDC syndrome of Guam and the cycad hypothesis. Neurology 70(21):1984–1990

    Article  PubMed  Google Scholar 

  • Stein PS (1995) Mycotoxins, general view, chemistry and structure. Toxicol Lett 82-83:843–851

    Article  Google Scholar 

  • Straub RH, Schradin C (2016) Chronic inflammatory systemic diseases: an evolutionary trade-off between acutely beneficial but chronically harmful programs. Evol Med Public Health 2016(1):37–51

  • Su FC, Goutman SA, Chernyak S, Mukherjee B, Callaghan BC, Batterman S, Feldman EL (2016) Association of environmental toxins with amyotrophic lateral sclerosis. JAMA Neurol 73(7):803–811

    Article  PubMed  PubMed Central  Google Scholar 

  • Sweeney MJ, Dobson DW (1998) Mycotoxin production by Aspergillus, Fusarium and Penicillium species. Int J Food Microbiol 43:141–158

    Article  CAS  PubMed  Google Scholar 

  • Tesauro M, Consonni M, Filippini T, Mazzini L, Pisano F et al (2017) Incidence of amyotrophic lateral sclerosis in the province of Novara, Italy, and possible role of environmental pollution. Amyotroph Lateral Scler Frontotemporal Degener 2:1–7

    Google Scholar 

  • Torbick N, Hession S, Stommel E, Caller T (2014) Mapping amyotrophic lateral sclerosis lake risk factors across northern New England. Int J Health Geogr 13(1):1

    Article  PubMed  PubMed Central  Google Scholar 

  • Torbick N, Ziniti B, Stommel E, Linder E, Andrew A, Caller T, Haney J, Bradley W, Henegan PL, Shi X (2018) Assessing cyanobacterial harmful algal blooms as risk factors for amyotrophic lateral sclerosis. Neurotox Res 33(1):199–212

    Article  PubMed  Google Scholar 

  • Uccelli R, Binazzi A, Altavista P, Belli S, Comba P, Mastrantonio M, Vanacore N (2007) Geographic distribution of amyotrophic lateral sclerosis through motor neuron disease mortality data. Eur J Epidemiol 22(11):781–790

    Article  PubMed  Google Scholar 

  • van der Graaff MM, de Jong JM, Baas F, de Visser M (2009) Upper motor neuron and extra-motor neuron involvement in amyotrophic lateral sclerosis: a clinical and brain imaging review. Neuromuscul Disord 19:53–58

    Article  PubMed  Google Scholar 

  • Vandoorne T, De Bock K, Van Den Bosch L (2018) Energy metabolism in ALS: an underappreciated opportunity? Acta Neuropathol 135(4):489–509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vinceti M, Bonvicini F, Rothman KJ, Vescovi L, Wang F (2010) The relation between amyotrophic lateral sclerosis and inorganic selenium in drinking water: a population-based case-control study. Environ Health 9:77–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wicks P, Ganesalingham J, Collin C, Prevett M, Leigh NP, al-Chalabi A (2007) Three soccer playing friends with simultaneous amyotrophic lateral sclerosis. Amyotroph Lateral Scler 8:177–179

    Article  PubMed  Google Scholar 

  • Zhang N, Zhang S, Borchert S, Richardson K, Schmid J (2011) High levels of a fungal superoxide dismutase and increased concentration of a PR-10 plant protein in associations between the endophytic fungus Neotyphodium lolii and ryegrass. Mol Plant-Microbe Interact 24(8):984–992

    Article  CAS  PubMed  Google Scholar 

  • Zufiría M, Gil-Bea FJ, Fernández-Torrón R, Poza JJ, Muñoz-Blanco JL, Rojas-García R, Riancho J, López de Munain A (2016) ALS: a bucket of genes, environment, metabolism and unknown ingredients. Prog Neurobiol 142:104–129

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter W. French.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

French, P.W., Ludowyke, R. & Guillemin, G.J. Fungal Neurotoxins and Sporadic Amyotrophic Lateral Sclerosis. Neurotox Res 35, 969–980 (2019). https://doi.org/10.1007/s12640-018-9980-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-018-9980-5

Keywords

  • Motor neuron disease
  • Amyotrophic lateral sclerosis
  • Mycotoxin
  • Fungi
  • Sporadic ALS