The Doerenkamp-Zbinden Chair of in-vitro
Toxicology and Biomedicine/Alternatives to Animal Experimentation

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Publications of Prof. Dr. Marcel Leist

General databases for complete reference of all publications

Medline: Marcel Leist

ResearcherID: D-2133-2010

Bibliometric information:

Citations: > 12000; h-index: 57 (e-index > 90); Sum of IF: > 900 (update 01. April 2013)


Selected recent publications (R = review)

Ramirez T, Daneshian M, Kamp H, Bois FY, Clench M, CoenM, Donley B, Fischer SM, Ekman DR, Fabian E, Guillou C, Heuer J, HogbergH, JungnickelH, KeunH, KrennrichG, KruppE, LuchA, NoorF, PeterE, RiefkeB, SeymourM, SkinnerN, Smirnova L, VerheijE, WagnerS, van Raavenzway B, Hartung T, Leist M (2013) Metabolomics in toxicology and preclinical research, a t4 workshop report                                                                                             
ALTEX 30, in press (R)

Leist, Hartung T (2013) Inflammatory findings on species extrapolations: humans are definitely no 70-kg mice. 
Arch Toxicol 87, 563-567 (R)

Krug A, Kolde R, Gaspar JA, Rempel E, Balmer NV, Meganathan K, Vojnits K, Baquié M, Waldmann T, Ensenat-Waser R, Jagtap S, Evans R, Julien Stephanie, Peterson H, Zagoura D, Kadereit S, Gerhard D, Sotiriadou I, Heke M, Natarajan K, Henry M, Winkler J, Marchan R, Stoppini L, Bosgra S, Westerhout J, Verwei M, Vilo J, Kortenkamp A, Hescheler J, Hothorn L, Bremer S, van Thriel C, Krause KH, Hengstler JG*, Rahnenführer J*, Leist M*, Sacchinidis A* (2013) Human embryonic stem cell derived test systems for developmental neurotoxicity: a transcriptomic approach    
Arch Toxicol 87, 123-143

Schildknecht S, Gerding HR, Karreman C, Drescher M, Lashuel HA, Outeiro TF, Di Monte DA, Leist M (2013) Oxidative and nitrative alpha synuclein modifications and proteostatic stress: implications for disease mechanisms and interventions in synucleinopathies                                                                                                                                
J Neurochem, in press (R)

Hoelting A, Scheinhardt B, Bondarenko O, Schildknecht S, Kapitza M, Tanavde V, Tan B, Lee QY, Mecking S, Leist M, Kadereit S (2013). A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles (Nano-DNT).
Arch Toxicol 87, 721-733

Balmer NV, Weng M, Zimmer B, Ivanova VN, Chambers SM, Nikolaeva E, Jagtap S, Sachinidis A, Hescheler J, Waldmann T, Leist M (2012). Epigenetic changes and disturbed neural development in a human embryonic stem cell-based model relating to the fetal valproate syndrome.                                                                    
Hum Mol Genet 21, 4104-4114

Zimmer B, Lee G, Stiegler NV, Meganathan K, Sacchinidis A, Studer L, Leist M (2012). Evaluation of developmental toxicants and signalling pathways in a functional test based on the migration of human neural crest cells.             
Env Health Perspect, 120, 1116 - 1122

Weng M, Zimmer B, Pöltl D, Brög M, Wüllner U, Waldmann T, Leist M (2012). Extensive transcriptional regulation of chromatin modifiers during human neurodevelopment.
PlosOne, 7, e36708

Scholz D, Chernyshova Y, Leist M (2013). Control of A-beta release from human neurons by differentiation status and RET signaling.                                                                                                                                           
Neurobiol Aging 34, 184-199

Kuegler PB, Baumann BA, Zimmer B, Keller S, Marx A, Kadereit S, Leist M (2012) GFAP-independent inflammatory competence and trophic functions of astrocytes generated from murine embryonic stem cells.            
Glia, 60, 218-228.

Pöltl D, Schildknecht S, Leist M (2012). Uncoupling of ATP-depletion and cell death in human dopaminergic neurons.  
NeuroToxicol, 33, 769 - 779.

Scholz D, Pöltl D, Genewsky A, Weng M, Waldmann T, Schildknecht S, Leist M (2011) Rapid, complete and large-scale generation of post-mitotic neurons from the human LUHMES cell line.                                                   
J Neurochem 119, 957-971.

Stiegler N, Krug A, Matt F, Leist M (2011) Assessment of chemical-induced impairment of human neurite outgrowth by multiparametric live cell imaging in high-density cultures.                                                                                                                                                   Toxicol Sci 121:73-87.

Zimmer B, Kuegler PB, Baudis B, Genewsky A, Tanavde V, Koh W, Tan B, Waldmann T, Kadereit S, Leist M(2011) Coordinated waves of gene expression during neuronal differentiation of embryonic stem cells as basis for novel approaches to developmental neurotoxicity testing.                                           
Cell Death Differ 18, 385-395.

Schildknecht S, Pape R, Müller R, Robotta M, Marquardt A, Bürkle A, Drescher M, Leist M(2011) Neuroprotection by minocycline caused by direct and specific scavenging of peroxynitrite.                                                                                                                                J Biol Chem, 286, 4991-5002.

Henn A, Lund S, Hedtjärn M, Schrattenholz A, Pörzgen P, and Leist M (2009). The suitability of BV2 cells as alternative model system for primary microglia cultures or animal experiments of brain inflammation
ALTEX 26, 83-94.


Selected reviews and concept papers:

Leist M, Lidbury BA, Yang C, Hayden PJ, Kelm JM, Ringeissen S, Detroyer A, Meunier JR, Rathman JF, Jackson GR, Stolper G, Hasiwa N (2012) Novel technologies and an overall strategy to allow hazard assessment and risk prediction of chemicals, cosmetics and drugs with animal-free methods
ALTEX 29, 373-388

Basketter DA, et al. (2012). A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing.     
ALTEX 29, 3-91

Leist M, Hasiwa N, Daneshian M, Hartung T (2012) Validation and quality control of replacement alternatives – current status and future challenges       
Toxicol Res 1, 8-22

Daneshian M, Akbarsha MA, Blaauboer B, Caloni F, Cosson P, Curren R, Goldberg A, Gruber F, Ohl F, Pfaller W, van der Valk J, Vinardell P, Zurlo J, Hartung T, Leist M (2011). A framework program for the teaching of alternative methods (replacement, reduction, refinement) to animal experimentation.     
ALTEX 28, 341 – 352

van Thriel C, Westerink R, Beste C, Bale AS, Lein PJ, Leist M (2011). Translating neurobehavioural endpoints of developmental neurotoxicity tests into in vitro assays and readouts,         
NeuroToxicol 33, 911-924

Kuegler PB, Zimmer B, Waldmann T, Baudis B, Ilmjarv S, Hescheler J, Gaughwin P, Brundin P, Mundy W, Bal-Price AK, Schrattenholz A, Krause KH, van Thriel C, Rao M, Kadereit S, Leist M (2010). Markers of murine embryonic and neural stem cells, neurons and astrocytes: reference points for developmental neurotoxicitiy testing – a review by the Translantic Think Tank for Toxicology (t4).                                                                                           
ALTEX 27, 17-42

Leist M, Efremova L, Karreman C (2010) Food for thought on considerations and guidelines for basic test method descriptions in toxicology.                                                                                                             
ALTEX 27, 309-317(R)

Leist M, Bremer S, Brundin P, Hescheler J, Kirkeby A, Krause KH, Pörzgen P, Pucéat M, Schmidt M, Schrattenholz A, Zak NB, Hentze H (2008). The biological and ethical basis of the use of embryonic stem cells for in vitro tests and cell therapy.    
ALTEX 25, 163-190

Leist M, Hartung T, Nicotera P (2008). The dawning of a new age of toxicology.           
ALTEX 25, 103-114.

Falsig J, van Beek J, Hermann C, Leist M. (2007) . – The molecular basis for detection of invading pathogens in the brain. .     
J Neurosci Res, 86, 1434-1447

Blomgren K, Leist M, Groc L. (2006). – Pathological apoptosis in the developing brain.           
Apoptosis 12, 993-1010.

Leist M, Jaattela M. (2002). - Burning up TNF toxicity for cancer therapy.         
Nature Medicine, 8, 667-668.

Leist M, Jaattela M. (2001). - Four deaths and a funeral: from caspases to alternative mechanisms. Nature Reviews Mol Cell Biol, 2, 589-598.

Nicotera P, Leist M, Manzo L. (1999). - Neuronal cell death: a demise with different shapes.     
Trends Pharmacol Sci., 20, 46-51.

Leist M, Künstle G, Gantner F, Wendel A. (1998). - Cytokine-mediated hepatic apoptosis.
Rev Physiol Biochem Pharmacol, 133, 109-155.

Leist M, Nicotera P. (1997). - Calcium and neuronal death.       
Rev. Physiol. Biochem. Pharmacol. 132, 79-125.



Parkinson’s disease, synuclein, dopaminergic degeneration

Robotta M, Hintze C, Schildknecht S, Zijlstra N, Jüngst C, Karreman C, Huber M, Leist M, Subramanian V, Drescher M (2012). Locally resolved membrane binding affinity of the N-terminus of α-Synuclein.                                        
Biochemistry, 51, 3960-3962

Vlad C, Lindner K, Karreman C, Schildknecht S, Leist M, Tomczyk N, Rontree J, Langridge J, Danzer K, Ciossek T, Petre A, Gross ML, Hengerer B, Przybylski M (2011). Autoproteolytic Fragments are Intermediates in the Oligomerization-Aggregation of Parkinson’s Disease Protein Alpha-Synuclein as Revealed by Ion Mobility Mass Spectometry.
ChemBioChem 16, 2740-2744

Schildknecht S, Poeltl D, Nagel DM, Matt F, Scholz D, Lotharius J, Salvo-Vargas A, Leist M (2009). Requirement of a dopaminergic neuronal phenotype for toxicity of low concentrations of 1-methyl-4-phenylpyridinium to human cells.  
Toxicol Appl Pharmacol, 241, 23-35.

Lotharius J, Falsig J, van Beek J, Payne S, Dringen R, Brundin P, Leist M. (2005). - Progressive degeneration of human mesencephalic neuron-derived cells triggered by dopaminedependent oxidative stress is dependent on the mixed lineage kinase pathway.
J Neurosci 25, 6329-6342.

Schierle GS, Hansson O, Leist M, Nicotera P, Widner H, Brundin P. (1999). - Caspase inhibition reduces apoptosis and increases survival of nigral transplants.
Nat Med 5, 97-100.

Leist M, Volbracht C, Fava E, Nicotera P. (1998). - 1-methyl-4-phenylpyridinium (MPP+) induces autocrine excitotoxicity, protease activation and neuronal apoptosis.
Mol Pharmacol 54, 789-801.

Leist M, Fava E, Montecucco C, Nicotera P. (1997). - Peroxynitrite and NO-donors induce neuronal apoptosis by stimulating autocrine excitotoxicity.
Eur. J. Neurosci. 9, 1488-1498.



Developmental toxicity

Zimmer B, Schildknecht S, Kuegler PB, Tanavde V, Kadereit S, Leist M (2011) Sensitivity of dopaminergic neuron differentiation from stem cells to chronic low-dose methylmercury exposure.
Toxicol Sci 121, 357 – 367.

Kadereit S, Zimmer B, van Thriel C, Hengstler JG, Leist M (2012). Compound selection for in vitro models of developmental neurotoxicity and prenatal neurotoxicity,   
Frontiers in Bioscience 17, 2442-2460



New toxicology, new cell models

Blaauboer BJ, Boekelheide K, Clewell HJ, Daneshian M, Dingemans MML, Goldberg AM, Heneweer M, Jaworska J, Kramer NI, Leist M, Seibert H, Testai E, Vandebriel RJ, Yager J, Zurlo J. (2012) The use of biomarkers of toxicity for integrating in vitro hazard estimates into risk assessment for humans.
ALTEX 29, 411-425

Schildknecht S, Kirner S, Henn A, Efremova L, Pape R, Fischer R, Leist M (2012). Characterization of the immortalized murine astrocyte cell line IMA2.1 as model system to study neuroinflammation and xenobiotic metabolism in the brain.    
ALTEX, 29, 261 – 274

Hasiwa N, Bailey J, Clausing P, Daneshian M, Eileraas M, Farkas S, Gyertyan I, Hubrecht R, Kobel W, Krummenacher G, Leist M, Lohi H, Miklosi A, Ohl F, Olejniczak K, Schmitt G, Sinnett-Smith P, Smith D, Wagner K, Yager JD, Zurlo J, Hartung T (2011). Critical evaluation of the use of dogs in biomedical research and testing in Europe.                    
ALTEX 28, 326–340

Daneshian M, Akbarsha MA, Blaauboer B, Caloni F, Cosson P, Curren R, Goldberg A, Gruber F, Ohl F, Pfaller W, van der Valk J, Vinardell P, Zurlo J, Hartung T, Leist M (2011). A framework program for the teaching of alternative methods (replacement, reduction, refinement) to animal experimentation.                                                             
ALTEX 28, 341–352.

Leist M, Efremova L, Karreman C (2010) Food for thought on considerations and guidelines for basic test method descriptions in toxicology.           
ALTEX 27, 309-317



Selected older papers: erythropoietin, neurodegeneration and stroke

Ghezzi P, Bernaudin M, Bianchi R, et al., Leist M, et al (2010). Erythropoietin: not just about erythropoiesis.
The Lancet 375, 2142.(R)

Volbracht C, Penzkofer S, Mansson D, Christensen KV, Fog K, Schildknecht S, Nielsen J, Leist M (2009). Measurement of cellular beta-site of APP cleaving enzyme 1 activity and its modulation in neuronal assay systems.
Anal Biochem 387, 220-234.

Kirkeby A, Torup L, Bochsen L, Kjalke M, Abel K, Theilgaard-Monch K, Johansson PI, Bjorn SE Gerwien J, Leist M (2008). High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO).
Thrombosis and Hemostasis 99, 720-728.

Wang L, Zhang ZG, Gregg SR, Zhang RL, Jiao Z, Letourneau Y, Liu X, Feng Y, Gerwien J, Torup L, Leist M, Noguchi CT, Chen ZY, Chopp M (2007). The sonic hedgehog pathway mediates carbamylated EPO enhanced proliferation and differentiation of adult neural progenitor cells.
J Biol Chem 282, 32462-32470.

van Beek J, Villa P, Larsen AK, Brines M, Cerami A, Leist M, Ghezzi P, Torup L (2007). Reduced functional deficits, neuroinflammation, and secondary tissue damage after treatment of stroke by nonerythropoietic erythropoietin derivatives.                                                                                                                            
J Cereb Blood Flow Metabol 27, 552-563.

Vergo S, Johansen JL, Leist M, Lotharius J (2007). Vesicular monoamine transporter 2 regulates the sensitivity of rat dopaminergic neurons to disturbed cytosolic dopamine levels.                                                             
Brain Res 1185, 18-32.

Selenica ML, Jensen HS, Larsen AK, Pedersen ML, Helboe L, Leist M, Lotharius J (2007). Efficacy of small-molecule glycogen synthase kinase-3 inhibitors in the postnatal rat model of tau hyperphosphorylation.                                                                                                             Br J Pharmacol 152, 959-79.

Berliocchi L, Fava E, Leist M, Horvat V, Dinsdale D, Read D, Nicotera P. (2005). - Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis.
J Cell Biol 168, 607-618.

Leist M et al. (2004). - Derivatives of erythropoietin that are tissue protective but not erythropoietic.
Science 305, 239-242.

Simon B, Malisan F, Testi R, Nicotera P, Leist M. (2002). - The disialoganglioside GD3 is released from microglia cells and induces oligodendrocyte apoptosis.         
Cell Death Differ 9, 758-767.

Hansson O, Petersen A, Leist M, Nicotera P, Castilho RF, Brundin P. (1999). - Transgenic mice expressing a Huntington’s disease mutation are protected from quinolinic acid-induced striatal excitotoxicity.
Proc. Natl. Acad. Sci. USA 96, 8727-8732.



Selected older papers: inflammation - glia

Henn A, Kirner S, Leist M (2011) TLR2 hypersensitivity of astrocytes as functional consequence of their previous inflammatory activation.                                                                                           
J Immunol 186, 3237-3247.

Christiansen SH, Selige J, Dunkern T, Rassov A, Leist M (2011) Combined anti-inflammatory effects of ß2-adrenergic agonists and PDE4 inhibitors on astrocytes by upregulation of intracellular cAMP.
Neurochem Int 59, 837 - 846.

Lund S, Porzgen P, Mortensen AL, Falsig J, Schrattenholz A, Hedtjarn M, Hagberg H, Leist M. (2006). - The dynamics of the LPS triggered inflammatory response of murine microglia under different culture and in vivo conditions.
J Neuroimmunol 180, 71-87

Falsig J, Porzgen P, Lotharius J, Leist M. (2004). - Specific modulation of astrocyte inflammation by inhibition of mixed lineage kinases with CEP1347.
J Immunol 173, 2762-2770.

Hirt UA, Leist M. (2003). - Rapid, non-inflammatory and PS-dependent phagocytic clearance of necrotic cells.
Cell Death Differ 10, 1156-1164.



Selected older papers: apoptosis and cell death regulation

Nylandsted J, Wick W, Hirt U, Brand K, Rohde M, Leist M, Weller M, Jaattela M. (2002). - Eradication of Gliobastoma and Breast and Colon Carcinoma Xenografts by Hsp70 Depletion.
Cancer Res 62, 7139-7124.

Foghsgaard L, Wissing D, Mauch D, Lademann U, Bastholm L, Boes M, Elling F, Jaattela M*, Leist M*. (2001). - Cathepsin B acts as a dominant execution protease in tumor cell apoptosis induced by tumor necrosis factor.
J Cell Biol 153, 999-1009. (* = shared senior/first authorship)

Volbracht C, Leist M, Kolb SA, Nicotera P (2001). Apoptosis in caspase-inhibited neurons.      
Mol. Med. 7, 36-48

Kuehnle S, Nicotera P, Wendel A, Leist M. (1999). - Prevention of endotoxin-induced lethality, but not of cytokine-induced liver apoptosis in poly (ADP-ribose) polymerase-deficient mice.
Biochem Biophys Res Commun 263, 433-438.

Hirt U, Gantner F, Leist M. (2000). - Phagocytosis of non-apoptotic cells dying by  caspaseindependent mechanisms.
J. Immunol. 164, 6520-6529.

Göhring F, Schwab B, Nicotera P, Leist M, Fackelmayer F. (1997). - The novel SAR binding domain of scaffold attachment factor A (SAF-A) is a target in apoptotic nuclear breakdown.                         EMBO J., 16, 7361-7371.

Leist M, Single B, Castoldi, AF, Kühnle S, Nicotera P. (1997). - Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis.
J. Exp. Med. 185, 1481-1486.



Selected older papers: toxicology and nutrition

Frimat J-P, Sisnaiske J, Subbiah S, Menne H, Godoy P, Lampen P, Leist M, Franzke J, Hengstler JG, van Thriel C, West J (2010). The network formation assay: A spatially standardized neurite outgrowth analytical display for neurotoxicity screening.
Lab Chip 10, 701-709.

Castro-Palomino J, Simon B, Speer O, Schmidt RR*, Leist M* (2001).  Synthesis of ganglioside GD3 and comparison to bovine brain GD3 with regard to mitochondrial uncoupling and oligodendrocyte apoptosis.           
Chemistry Eur J 7, 2178-2184

Suter M, Reme C, Grimm C, Wenzel A, Jaattela M, Esser P, Kociok N, Leist M, Richter C (2000). Age-related macular degeneration: the lipofuscin component A2E releases pro-apoptotic proteins from mitochondria and induces apoptosis in mammalian retinal epithelial cells.          
J Biol Chem 275, 39625-39630.

Stridh H, Fava E, Single B, Nicotera P, Orrenius S, Leist M (1999). Tributyltin-induced apoptosis requires glycolytic adenosine triphosphate production.   
Chem. Res. Toxicol. 12, 874-882.

Volbracht C, Leist M, Nicotera P (1999). ATP controls neuronal apoptosis triggered by microtubule breakdown or potassium deprivation.          
Mol. Med. 5, 477-489

Leist M, Raab B, Maurer S, Brigelius-Flohé R. (1996). - Conventional cell culture media do not adequately supply cells with antioxidants and thus facilitate peroxide-induced genotoxicity.
Free. Rad. Biol. Med. 21, 297-306.

Brigelius-Flohé R, Lötzer K, Maurer S, Schultz M, Leist M. (1996). - Utilization of selenium from different chemical entities for selenoprotein biosynthesis by mammalian cell lines.                  Biofactors 5, 125-131.

Leist M, Ayrton AD, Ioannides C. (1992). - A cytosolic oxygenase activity involved in the bioactivation of 2-aminofluorene.
Toxicol. 71, 7-20.



Selected older papers: liver degeneration

Latta M, Künstle G, Wendel A*, Leist M*. (2000). - Metabolic depletion of adenosine triphosphate by fructose inversely controls CD95- and TNF-R1-mediated hepatic apoptosis.
J. Exp. Med. 191, 1975-1985. * = shared senior/first authorship

Leist M, Gantner F, Naumann H, Vogt K, Bluethmann H, Brigelius-Flohé R, Nicotera P, Volk D, Wendel A. (1997). - Tumor necrosis factor-induced apoptosis during poisoning with hepatotoxins.
Gastroenterol. 112, 923-935.

Leist M, Gantner F, Künstle G, Bohlinger I, Bluethmann H, Tiegs G, Wendel A. (1996). - The 55 kDa tumor necrosis factor receptor and CD95 independently signal murine hepatocyte apoptosis and subsequent liver failure.
Mol. Med. 2, 109-124.

Leist M, Gantner F, Bohlinger I, Germann P G, Tiegs G, Wendel A. (1995). - TNF-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models.
Am. J. Pathol. 146, 1220-1234.

Leist M, Gantner F, Bohlinger I, Germann P G, Tiegs G, Wendel A. (1994). - Murine hepatocyte apoptosis induced in vitro and in vivo by TNF-α requires transcriptional arrest.
J. Immunol. 153, 1778-1787.