Article
Food Science & Technology
Jake P. Violi, Lisa Pu, Sercan Pravadali-Cekic, David P. Bishop, Connor R. Phillips, Kenneth J. Rodgers
Summary: The cyanobacterial neurotoxin BMAA had a profound effect on intracellular amino acid levels in human neuroblastoma cells at specific time points, but homeostasis was restored in most cases. Supplementation with L-serine protected against BMAA toxicity. Amino acids potentially involved in protection against BMAA-induced oxidation were depleted in cells at later time points.
Article
Clinical Neurology
Tiziana Petrozziello, Ana C. Amaral, Simon Dujardin, Sali M. K. Farhan, James Chan, Bianca A. Trombetta, Pia Kivisakk, Alexandra N. Mills, Evan A. Bordt, Spencer E. Kim, Patrick M. Dooley, Caitlin Commins, Theresa R. Connors, Derek H. Oakley, Anubrata Ghosal, Teresa Gomez-Isla, Bradley T. Hyman, Steven E. Arnold, Tara Spires-Jones, Merit E. Cudkowicz, James D. Berry, Ghazaleh Sadri-Vakili
Summary: This study found alterations in tau phosphorylation in post-mortem motor cortex of ALS patients, especially increased total tau and pTau-S396 in C9ORF72-ALS. Levels of total tau in cerebrospinal fluid were associated with disease progression speed, while the pTau-T181:tau ratio correlated with disease progression speed.
Article
Neurosciences
Tiziana Petrozziello, Evan A. Bordt, Alexandra N. Mills, Spencer E. Kim, Ellen Sapp, Benjamin A. Devlin, Abigail A. Obeng-Marnu, Sali M. K. Farhan, Ana C. Amaral, Simon Dujardin, Patrick M. Dooley, Christopher Henstridge, Derek H. Oakley, Andreas Neueder, Bradley T. Hyman, Tara L. Spires-Jones, Staci D. Bilbo, Khashayar Vakili, Merit E. Cudkowicz, James D. Berry, Marian DiFiglia, M. Catarina Silva, Stephen J. Haggarty, Ghazaleh Sadri-Vakili
Summary: Research suggests that increased levels of hyperphosphorylated tau may lead to mitochondrial fragmentation and oxidative stress in amyotrophic lateral sclerosis (ALS); reducing tau levels could potentially alleviate mitochondrial dysfunction in ALS.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Soe Maung Maung Phone Myint, Liou Y. Sun
Summary: L-serine is a crucial amino acid involved in protein synthesis, cell proliferation, development, and sphingolipid formation in the central nervous system. It has neuroprotective and anti-inflammatory effects by activating glycine receptors and upregulating PPAR-γ. L-serine has potential as a protective agent in various neurological diseases and neurodegenerative disorders.
Review
Biochemistry & Molecular Biology
Paola Sini, Thi Bang Chau Dang, Milena Fais, Manuela Galioto, Bachisio Mario Padedda, Antonella Luglie, Ciro Iaccarino, Claudia Crosio
Summary: The prevalence of neurodegenerative diseases is increasing due to longer lifespans, but the causes and mechanisms are not fully understood, and effective treatments are lacking. Genetic susceptibility and environmental factors are believed to play a role in the development of diseases like Alzheimer's and Parkinson's, with cyanotoxins produced by cyanobacteria possibly acting as important environmental triggers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Environmental Sciences
Kate Samardzic, Joel R. Steele, Jake P. Violi, Anne Colville, Simon M. Mitrovic, Kenneth J. Rodgers
Summary: The study showed that the growth of alfalfa roots was significantly inhibited by BMAA and DAB, with higher levels detected in the plant. This suggests a potential pathway for NPAAs to enter the food chain through contaminated irrigation water, posing a risk for human exposure.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Biochemistry & Molecular Biology
Sercan Pravadali-Cekic, Aleksandar Vojvodic, Jake P. Violi, Simon M. Mitrovic, Kenneth J. Rodgers, David P. Bishop
Summary: This study presents a newly developed and validated method for the detection and quantification of BMAA, its isomers, and major MCs using RP LC-MS/MS. The application of this method on a culture of Microcystis aeruginosa resulted in the simultaneous detection of 2,4-DAB and MC-YR. The study provides a unified method for the quantitative analysis of these cyanotoxins in natural environmental samples.
Article
Marine & Freshwater Biology
Zi-Qian Wang, Cheng-Cai Zhang
Summary: In this study, the authors demonstrate that the system responsible for modifying ANN-decoding tRNAs is involved in the sensitivity of cyanobacteria to the environmental neurotoxin BMAA. The study also reveals that both BMAA and inactivation of the t(6)A biosynthesis pathway affect translational fidelity and ribosome assembly. BMAA-resistant mutants screening is an effective method for gaining insight into the toxic mechanisms of BMAA.
AQUATIC TOXICOLOGY
(2022)
Article
Clinical Neurology
Philippe Corcia, Pascal Lejeune, Patrick Vourc'h, Stephane Beltran, Anne-Sophie Piegay, Helene Blasco, Vincent Meininger
Summary: This study characterized the prototypical phenotype of patients with amyotrophic lateral sclerosis (ALS) associated with PFN1 mutations and identified clinical indications for testing mutations in this gene. The main clinical findings for familial ALS linked to PFN1 were identified as pedigrees with over five cases, an onset age around 50 years, onset in the lower limbs, and the absence of cognitive impairment. The similarities with other ALS mutations prompt a review of ALS classifications based on both phenotype and genotype.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Adam W. Quinn, Connor R. Phillips, Jake P. Violi, Joel R. Steele, Michael S. Johnson, Mika T. Westerhausen, Kenneth J. Rodgers
Summary: BMAA, a cyanobacterial non-protein amino acid, was first linked to neurological disorders on Guam in the 1950s and is still being studied as a potential factor in ALS. Its toxicity mechanisms include effects on glutamate receptors, competition with cysteine, and oxidative stress generation.
Article
Pharmacology & Pharmacy
J. S. Dileep Kumar, Andrei Molotkov, Jongho Kim, Patrick Carberry, Sidney Idumonyi, John Castrillon, Karen Duff, Neil A. Shneider, Akiva Mintz
Summary: In this study, we observed a decrease in microtubule binding of [C-11]MPC-6827 in transgenic mouse models of Alzheimer's disease and amyotrophic lateral sclerosis. These findings suggest that [C-11]MPC-6827 could potentially serve as a PET ligand for imaging Alzheimer's disease, ALS, and other neurodegenerative diseases.
PHARMACOLOGICAL REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Siobhan J. Peters, Kenneth J. Rodgers, Simon M. Mitrovic, David P. Bishop
Summary: This study utilized modern analytical techniques to monitor the concentrations of BMAA and its isomers during a cyanobacteria bloom event, revealing a decreasing trend in BMAA concentration as the bloom progressed, while its isomers did not follow the same decreasing pattern.
Review
Cell Biology
Lana Kupershmidt, Moussa B. H. Youdim
Summary: Researchers have developed multi-target, non-toxic, lipophilic, brain-permeable compounds with iron chelation and anti-apoptotic properties for the treatment of neurological disorders. These compounds have been tested in animal and cellular models and have shown neuroprotective effects by attenuating neurodegenerative pathology, promoting positive behavior changes, and up-regulating neuroprotective signaling pathways.
Review
Clinical Neurology
Thomas H. Julian, Sarah Boddy, Mahjabin Islam, Julian Kurz, Katherine J. Whittaker, Tobias Moll, Calum Harvey, Sai Zhang, Michael P. Snyder, Christopher McDermott, Johnathan Cooper-Knock, Pamela J. Shaw
Summary: Mendelian randomization studies on amyotrophic lateral sclerosis show a causal link between blood lipids and the disease risk, while factors like smoking and immune function require further investigation for confirmation. The use of high methodological standards and replication across different datasets are essential for reliable results in Mendelian randomization studies.
Article
Biochemistry & Molecular Biology
Andrea Mastrangelo, Veria Vacchiano, Corrado Zenesini, Edoardo Ruggeri, Simone Baiardi, Arianna Cherici, Patrizia Avoni, Barbara Polischi, Francesca Santoro, Sabina Capellari, Rocco Liguori, Piero Parchi
Summary: Recent studies have shown that ALS patients have higher levels of plasma GFAP compared to controls, and this marker is associated with cognitive decline. Plasma GFAP is an accurate biomarker for identifying Alzheimer's disease co-pathology in ALS, which can influence the cognitive phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
David A. Davis, Paul Alan Cox, Sandra Anne Banack, Patricia D. Lecusay, Susanna P. Garamszegi, Matthew J. Hagan, James T. Powell, James S. Metcalf, Roberta M. Palmour, Amy Beierschmitt, Walter G. Bradley, Deborah C. Mash
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2020)
Article
Neurosciences
Erika J. Wolf, Ci-Di Chen, Xiang Zhao, Zhenwei Zhou, Filomene G. Morrison, Nikolaos P. Daskalakis, Annjanette Stone, Steven Schichman, Jaclyn Garza Grenier, Dana Fein-Schaffer, Bertrand R. Huber, Carmela R. Abraham, Mark W. Miller, Mark W. Logue
Summary: This study found that a specific polymorphism of the longevity gene klotho (KL), rs9315202, interacted with posttraumatic stress disorder (PTSD) to predict advanced epigenetic age in the motor cortex. Additionally, alcohol abuse was associated with advanced epigenetic age in the motor cortex. The results suggest that alterations in the KL gene may operate through long noncoding RNA to affect KL gene expression.
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Matthew J. Girgenti, Jiawei Wang, Dingjue Ji, Dianne A. Cruz, Murray B. Stein, Joel Gelernter, Keith A. Young, Bertrand R. Huber, Douglas E. Williamson, Matthew J. Friedman, John H. Krystal, Hongyu Zhao, Ronald S. Duman, Ronald S. Duman
Summary: This study provides comprehensive insights into the molecular pathology of post-traumatic stress disorder (PTSD) through transcriptome analysis of postmortem brains, revealing extensive remodeling of gene expression networks and identifying genetic susceptibility factors, as well as marked transcriptional sexual dimorphism. Additionally, comparison with major depressive disorder cohorts shows significant differences between the molecular profiles of individuals with PTSD and major depressive disorder despite their high comorbidity, supporting the notion that PTSD has distinct molecular determinants.
NATURE NEUROSCIENCE
(2021)
Editorial Material
Neurosciences
Paul Alan Cox
Summary: Studies in this volume explore the various forms of BMAA and its potential neurotoxic risks from environmental exposures. Discrepancies in the detection and quantification of BMAA across different laboratories may stem from the use of varying analytical methods.
NEUROTOXICITY RESEARCH
(2021)
Review
Neurosciences
R. A. Dunlop, S. A. Banack, S. L. Bishop, J. S. Metcalf, S. J. Murch, D. A. Davis, E. W. Stommel, O. Karlsson, E. B. Brittebo, A. D. Chatziefthimiou, V. X. Tan, G. G. Guillemin, P. A. Cox, D. C. Mash, W. G. Bradley
Summary: Chernoff et al. criticize the hypothesis of BMAA exposure as a risk factor for neurodegenerative diseases, pointing out errors in their critique such as selective citation of literature and misattribution of methods. Although uncertainties exist in the research field of chronic exposure to BMAA causing neurodegenerative diseases, an increasing body of evidence suggests this possibility.
NEUROTOXICITY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Olivia M. de Goede, Daniel C. Nachun, Nicole M. Ferraro, Michael J. Gloudemans, Abhiram S. Rao, Craig Smail, Tiffany Y. Eulalio, Francois Aguet, Bernard Ng, Jishu Xu, Alvaro N. Barbeira, Stephane E. Castel, Sarah Kim-Hellmuth, YoSon Park, Alexandra J. Scott, Benjamin J. Strober, Christopher D. Brown, Xiaoquan Wen, Ira M. Hall, Alexis Battle, Tuuli Lappalainen, Hae Kyung Im, Kristin G. Ardlie, Sara Mostafavi, Thomas Quertermous, Karla Kirkegaard, Stephen B. Montgomery
Summary: This study systematically characterized 14,100 lncRNA genes across 49 tissues for 101 complex genetic traits using GTEx project data, identifying 1,432 lncRNA gene-trait associations, 800 of which were not explained by neighboring protein-coding genes. The findings revealed associations between lncRNA and various diseases and traits.
Review
Food Science & Technology
James S. Metcalf, Maeve Tischbein, Paul Alan Cox, Elijah W. Stommel
Summary: This review discusses the neurotoxic effects of cyanobacterial toxins on the central nervous system, including issues of acute and chronic exposure, detection, and remediation. Inhalation of toxins through the air may be a significant exposure pathway, and cyanobacterial toxins may have neurotoxic properties beyond their traditional toxicities.
Article
Neurosciences
Mark W. Logue, Zhenwei Zhou, Filomene G. Morrison, Erika J. Wolf, Nikolaos P. Daskalakis, Christos Chatzinakos, Foivos Georgiadis, Adam T. Labadorf, Matthew J. Girgenti, Keith A. Young, Douglas E. Williamson, Xiang Zhao, Jaclyn Garza Grenier, Bertrand Russell Huber, Mark W. Miller
Summary: This study identified several novel PTSD-associated genes and brain region-specific PTSD-associated immune-related networks. Replication of dlPFC associations in an independent cohort from a recent study showed a strong correlation between the dlPFC PTSD effect sizes for significant genes in the two studies.
NEUROBIOLOGY OF STRESS
(2021)
Article
Plant Sciences
Samantha L. Gerlach, Rachael A. Dunlop, James S. Metcalf, Sandra A. Banack, Paul Alan Cox
Summary: This study found that cyclotides have cytotoxic effects on human brain astrocytoma cells and human bone marrow derived neuroblastoma cells and can increase TMZ-induced cell death. The results suggest that cyclotides may serve as adjuvants to TMZ chemotherapy.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Food Science & Technology
David A. Davis, Susanna P. Garamszegi, Sandra Anne Banack, Patrick D. Dooley, Thomas M. Coyne, Dylan W. McLean, David S. Rotstein, Deborah C. Mash, Paul Alan Cox
Summary: The study found that dolphins exposed to BMAA and MeHg may lead to changes in neuropathology, including lesions similar to AD. The results suggest that dolphins exposed to BMAA and MeHg displayed similar neurodegenerative disease features as AD patients.
Article
Neurosciences
Erika J. Wolf, Xiang Zhao, Sage E. Hawn, Filomene G. Morrison, Zhenwei Zhou, Dana Fein-Schaffer, Bertrand Huber, Mark W. Miller, Mark W. Logue
Summary: Psychiatric stress is associated with accelerated epigenetic aging and increased expression of inflammation genes in the brain, potentially linking accelerated cellular aging to premature disease onset and neurodegeneration. This suggests that anti-inflammatory interventions may be crucial in preventing or delaying cellular aging and increasing resilience to diseases of aging.
NEUROBIOLOGY OF STRESS
(2021)
Article
Multidisciplinary Sciences
Sandra Anne Banack, Aleksandra C. Stark, Paul Alan Cox
Summary: This study aimed to identify a usable biomarker for early-stage Alzheimer's disease (AD) patients from blood samples. By comparing metabolites in blood plasma between early-stage AD patients and healthy controls, the study found that the concentration of 2-aminoethyl dihydrogen phosphate normalized by taurine concentration could distinguish early-stage AD patients. This potential biomarker could supplement clinical diagnosis for early detection of Alzheimer's disease.
Article
Psychology, Clinical
Xiang Zhao, Mark W. Logue, Sage E. Hawn, Zoe E. Neale, Zhenwei Zhou, Bertrand R. Huber, Mark W. Miller, Erika J. Wolf
Summary: This study suggests that psychiatric disorders are associated with DNA methylation age, and inflammation and immune system dysregulation play a significant role in the link between psychopathology and cellular aging.
DEPRESSION AND ANXIETY
(2022)
Article
Psychiatry
Sheila T. Nagamatsu, Gregory Rompala, Yasmin L. Hurd, Diana L. Nunez-Rios, Janitza L. Montalvo-Ortiz
Summary: This study investigates the role of mCpHs in OUD and identifies important biological pathways and drug targets associated with the disorder in the human postmortem orbital frontal cortex.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Rachael Anne Dunlop, Sandra Anne Banack, Paul Alan Cox
Summary: MicroRNAs(miRNAs) have potential as diagnostic and prognostic biomarkers, but inconsistencies across studies have hindered their clinical application. Differences in miRNAs associated with specific diseases and regulation direction reflect the heterogeneity of pathologies or different protocols. This study aimed to determine if a unique extracellular vesicle fraction could improve the reproducibility of miRNA fingerprint diagnostic of ALS.