Review
Cell Biology
Bochao Liu, Mo Li, Lingyan Zhang, Zhiguo Chen, Paul Lu
Summary: Amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, is a degenerative disorder that leads to muscle wasting and paralysis, with no effective treatment options currently available. Stem cell therapy shows promise as a potential therapeutic strategy for this debilitating condition, offering a novel approach to replacing lost motor neurons and potentially restoring motor control in patients.
NEURAL REGENERATION RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Mireia Herrando-Grabulosa, Nuria Gaja-Capdevila, Jose M. Vela, Xavier Navarro
Summary: ALS is an adult disease with poor prognosis and no effective cure. The pathogenic mechanisms involved include glutamate excitotoxicity, mitochondrial alterations, and inflammation.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Belen Proano, Julia Casani-Cubel, Maria Benlloch, Ana Rodriguez-Mateos, Esther Navarro-Illana, Jose Maria Lajara-Romance, Jose Enrique de la Rubia Orti
Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with no medical cure. Dutasteride, a potential treatment molecule, has shown neuroprotective, antioxidant, and anti-inflammatory effects in ALS.
Review
Cell & Tissue Engineering
Ameneh Shokati, Abdorreza Naser Moghadasi, Mohsen Nikbakht, Mohammad Ali Sahraian, Seyed Asadollah Mousavi, Jafar Ai
Summary: Multiple sclerosis (MS) is a chronic central nervous system disease with limited treatment options, leading researchers to explore new therapies such as mesenchymal stromal cell (MSC) transplantation. Allogeneic MSCs are suggested as a potential novel solution for MS therapy as an alternative to autologous MSCs.
STEM CELL RESEARCH & THERAPY
(2021)
Review
Cell Biology
Gabriele Bonaventura, Antonio Munafo, Carlo Maria Bellanca, Valentina La Cognata, Rosario Iemmolo, Giuseppe Antonino Attaguile, Rosaria Di Mauro, Giulia Di Benedetto, Giuseppina Cantarella, Maria Luisa Barcellona, Sebastiano Cavallaro, Renato Bernardini
Summary: Stem cells offer potential therapeutic strategies for severe neurodegenerative disorders by replacing damaged neuronal cells and creating a neuro-protective environment through the release of bioactive molecules. The field of stem cells is advancing with the introduction of new technologies and alternative cell tissue sources, pointing towards exciting frontiers in research for treatment options of these diseases.
Correction
Multidisciplinary Sciences
Toru Yamashita, Yoshihiro Kushida, Shohei Wakao, Koh Tadokoro, Emi Nomura, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Mari Dezawa, Koji Abe
Summary: The amended version of this paper has been published and can be accessed through a link at the top of the paper.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Aude Chiot, Shanu F. Roemer, Lisa Ryner, Alina Bogachuk, Katie Emberley, Dillon Brownell, Gisselle A. Jimenez, Michael Leviten, Randall Woltjer, Dennis W. Dickson, Lawrence Steinman, Bahareh Ajami
Summary: This study found that alpha 5 integrin is prominently expressed in motor pathways and perivascular zones associated with the blood-brain barrier in ALS patients and mouse models. Treatment with an antibody against alpha 5 integrin improved survival and motor function in the mouse model.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Immunology
Zongzhi Jiang, Ziyi Wang, Xiaojing Wei, Xue-Fan Yu
Summary: This review article summarizes the role and application of inflammatory markers in amyotrophic lateral sclerosis (ALS). Inflammatory molecules and proteins play a key role in the pathogenesis of ALS and may serve as indicators for predicting patient survival and evaluating treatment response. Furthermore, inflammatory markers have the potential to be used as new therapeutic targets and strategies to expand the therapeutic interventions for ALS.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Kiyoung Kim
Summary: ALS is a rare neurological disorder characterized by a deficiency in the antioxidant tripeptide glutathione (GSH). Imbalanced GSH homeostasis and its molecular characteristics play crucial roles in ALS development. Studies have shown that GSH metabolism and redox status are associated with neuronal toxicity in ALS.
Review
Cell Biology
Sandra M. Martin-Guerrero, Andrea Markovinovic, Gabor M. Morotz, Shaakir Salam, Wendy Noble, Christopher C. J. Miller
Summary: Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two major neurodegenerative diseases and are now known to be associated with each other. Currently, there are no cures or effective treatments for FTD or ALS, necessitating the identification of new therapeutic targets. Recent studies have shown that the damaged signaling between the endoplasmic reticulum (ER) and mitochondria plays a role in FTD/ALS. Restoring this disrupted signaling may have the potential to correct other damaged features of FTD/ALS.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Medicine, General & Internal
Julia Costa, Marta Gromicho, Ana Pronto-Laborinho, Conceicao Almeida, Ricardo A. Gomes, Ana C. L. Guerreiro, Abel Oliva, Susana Pinto, Mamede de Carvalho
Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing motor neuron dysfunction, with chitinases like Chitotriosidase and chitinase-3-like proteins showing potential as important biomarkers for disease progression in ALS patients.
Review
Cell Biology
Santiago E. Charif, M. Florencia Vassallu, Lara Salvanal, Lionel M. Igaz
Summary: Protein synthesis is crucial for cell metabolism, and protein imbalances can cause neurodegenerative diseases. Neurons are particularly susceptible to the harmful effects of protein overload, and with age, proteostatic mechanisms become less effective. Research on therapeutic compounds aimed at restoring protein balance is of great importance.
NEURAL REGENERATION RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Barbara Teruel-Pena, Jose Luis Gomez-Urquiza, Nora Suleiman-Martos, Isabel Prieto, Francisco Jose Garcia-Cozar, Manuel Ramirez-Sanchez, Carmen Fernandez-Martos, German Dominguez-Vias
Summary: Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of motor neurons and biomarkers for ALS are important for disease detection and therapeutic targets. This study conducted a systematic review and meta-analyses of genetic loci associated with ALS using genome-wide association studies (GWASs). Aminopeptidases were identified as possible biomarkers, but the meta-analyses did not show a risk association between the genetic variation rs1060404 in the DPP6 gene and ALS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Mariana A. Amoros, Esther S. Choi, Axel R. Cofre, Nikolay Dokholyan, Marcelo Duzzioni
Summary: The development and study of cell culture models that replicate the characteristics of nervous system diseases are crucial for drug discovery and treatment advancement. Induced pluripotent stem cell (iPSC) technology provides an opportunity to create neuronal pathology models due to the difficulty in obtaining neuronal tissues. This article focuses on iPSCs derived from patients with amyotrophic lateral sclerosis (ALS) and explores the process of obtaining motor neuron-derived iPSCs (iPSC-MNs), current 3D models, and the potential of bioinformatics in finding new pharmacological treatments.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Chemistry, Medicinal
Jessica Merjane, Roger Chung, Rickie Patani, Leszek Lisowski
Summary: Despite the mysterious etiology, differentiated treatments are required for ALS to address both familial and sporadic cases. Targeting mechanisms of defective protein homeostasis and RNA processing, as well as exploring the use of gene therapy through adeno-associated virus (AAV) for gene delivery to the CNS, might provide potential therapeutic interventions. Overall, there is a strong need for disease modifying treatments for ALS that can effectively treat the full spectrum of cases.
MEDICINAL RESEARCH REVIEWS
(2023)
Review
Neurosciences
Phillippa J. Carling, Heather Mortiboys, Claire Green, Simeon Mihaylov, Cynthia Sandor, Aurelie Schwartzentruber, Rosie Taylor, Wenbin Wei, Chris Hastings, Siew Wong, Christine Lo, Samuel Evetts, Hannah Clemmens, Matthew Wyles, Sam Willcox, Thomas Payne, Rachel Hughes, Laura Ferraiuolo, Caleb Webber, Winston Hide, Richard Wade-Martins, Kevin Talbot, Michele T. Hu, Oliver Bandmann
PROGRESS IN NEUROBIOLOGY
(2020)
Review
Clinical Neurology
Monika A. Myszczynska, Poojitha N. Ojamies, Alix M. B. Lacoste, Daniel Neil, Amir Saffari, Richard Mead, Guillaume M. Hautbergue, Joanna D. Holbrook, Laura Ferraiuolo
NATURE REVIEWS NEUROLOGY
(2020)
Article
Health Care Sciences & Services
Simon M. Bell, Matteo De Marco, Katy Barnes, Pamela J. Shaw, Laura Ferraiuolo, Daniel J. Blackburn, Heather Mortiboys, Annalena Venneri
JOURNAL OF PERSONALIZED MEDICINE
(2020)
Article
Multidisciplinary Sciences
Aurelie Schwartzentruber, Camilla Boschian, Fernanda Martins Lopes, Monika A. Myszczynska, Elizabeth J. New, Julien Beyrath, Jan Smeitink, Laura Ferraiuolo, Heather Mortiboys
SCIENTIFIC REPORTS
(2020)
Article
Cell Biology
Noemi Gatto, Cleide Dos Santos Souza, Allan C. Shaw, Simon M. Bell, Monika A. Myszczynska, Samantha Powers, Kathrin Meyer, Lydia M. Castelli, Evangelia Karyka, Heather Mortiboys, Mimoun Azzouz, Guillaume M. Hautbergue, Nora M. Markus, Pamela J. Shaw, Laura Ferraiuolo
Summary: The study found that induced astrocytes from fibroblast donors in childhood or adulthood displayed age-related transcriptional differences and functional divergences, including altered nuclear compartmentalisation, nucleocytoplasmic shuttling properties, oxidative stress response, and DNA damage response. These results indicate that induced neural progenitor cell-derived astrocytes are a unique and valuable model for studying human astrocyte function.
Review
Biochemistry & Molecular Biology
Simon M. Bell, Katy Barnes, Matteo De Marco, Pamela J. Shaw, Laura Ferraiuolo, Daniel J. Blackburn, Annalena Venneri, Heather Mortiboys
Summary: Alzheimer's disease is the most common cause of dementia globally, characterized by amyloid beta and tau protein accumulation with currently no approved treatment. In addition to protein aggregation, other pathological changes and early alterations in mitochondrial function are present. Mitochondrial dysfunction caused by amyloid and tau may serve as potential biomarkers for early detection of AD, but further research with larger patient cohorts is needed for clinical application.
Review
Biochemistry & Molecular Biology
Jannigje Rachel Kok, Nelma M. Palminha, Cleide Dos Santos Souza, Sherif F. El-Khamisy, Laura Ferraiuolo
Summary: Increasing evidence supports the involvement of DNA damage in various neurodegenerative diseases, including ALS. DNA damage in ALS may vary between genetic subgroups, particularly with repeat expansion in the C9ORF72 gene. Several genes associated with ALS, such as TARDBP, FUS, NEK1, SQSTM1 and SETX, may contribute to neuronal death by affecting DNA repair and the DNA damage response.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Neurosciences
Laura Ferraiuolo, Nicholas J. Maragakis
Summary: Research has shown that multiple cell types contribute to ALS progression, but in vivo models have limitations. Human induced pluripotent stem cell technology is a powerful tool for studying disease mechanisms and drug discovery in ALS research.
NEUROSCIENCE LETTERS
(2021)
Article
Medicine, Research & Experimental
Yuri Ciervo, Noemi Gatto, Chloe Allen, Andrew Grierson, Laura Ferraiuolo, Richard J. Mead, Pamela J. Shaw
Summary: Mouse adipose-derived stem cells (ADSCs) injected into ALS mice improved motor function, delayed disease onset, and protected motor neurons by reducing glial activation. In vitro studies also showed that ADSCs rescued motor neurons from ALS astrocytes' neurotoxicity and reduced the inflammatory response in ALS astrocytes. Additionally, ADSCs were found to protect motor neurons from neurotoxicity mediated by human induced astrocytes derived from ALS patients, suggesting a potential therapeutic translation of ADSCs for human ALS.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Nelma M. Palminha, Cleide Dos Santos Souza, Jon Griffin, Chunyan Liao, Laura Ferraiuolo, Sherif F. El-Khamisy
Summary: This study reveals that TOP1-mediated chromosomal breaks in Huntington's disease (HD) can lead to defective recruitment of 53BP1, affecting DNA repair. The defect is caused by reduced H2A ubiquitination due to limited RNF168 activity, resulting from an increased interaction with p62. Depletion of p62 or disruption of RNF168-p62 interaction restores 53BP1 enrichment and DNA repair in HD models.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Cell Biology
Francesca Provenzano, Sophie Nyberg, Debora Giunti, Carola Torazza, Benedetta Parodi, Tiziana Bonifacino, Cesare Usai, Nicole Kerlero de Rosbo, Marco Milanese, Antonio Uccelli, Pamela J. Shaw, Laura Ferraiuolo, Giambattista Bonanno
Summary: This study found that extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) can reduce the toxic phenotype and neurotoxicity of astrocytes in amyotrophic lateral sclerosis (ALS), suggesting a potential therapeutic strategy.
Review
Biochemistry & Molecular Biology
Ana Aragon-Gonzalez, Pamela J. Shaw, Laura Ferraiuolo
Summary: This review provides a detailed explanation of the importance of maintaining a healthy blood-brain barrier (BBB) for disease prevention and the main pathomechanisms affecting BBB function. Barrier disruption is a common feature in both neurodegenerative and neurodevelopmental diseases. Potential therapies based on the BBB properties, such as molecular Trojan horses, and innovative treatments like stem cell therapies are being reviewed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Meeting Abstract
Clinical Neurology
Martyna Matuszyk, Laura Ferraiuolo, Alexander Taylor, Peter Davies, Rosemary Staniforth, Claire Garwood, Stephen Wharton
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Biology
Tom Leah, Irina Vazquez-Villasenor, Laura Ferraiuolo, Stephen B. Wharton, Heather Mortiboys
Summary: Various cell models, such as primary patient derived cells, SHSY-5Y cells and in vivo models, have been extensively utilized to study the contribution of mitochondrial dysfunction in Parkinson's disease.
Meeting Abstract
Clinical Neurology
Simon Bell, Matteo De Marco, Katy Barnes, Pamela Shaw, Laura Ferraiuolo, Daniel Blackburn, Heather Mortiboys, Annalena Venneri
