Journal Menu► ▼ Journal Menu
Journal Browser► ▼ Journal Browser
Special Issue "Amyotrophic Lateral Sclerosis: Understanding the Pathogenetic Mechanisms for the Development of New Therapies"
A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".
Deadline for manuscript submissions: 20 July 2023 | Viewed by 10768
Special Issue Editor
Interests: amyotrophic lateral sclerosis; animal models; immune system; peripheral nervous system; skeletal muscle
Special Issue Information
Over the past twenty years, we have seen a dramatic increase in knowledge of Amyotrophic Lateral Sclerosis. Using animal and in vitro models has allowed for the identification of several mechanisms that contribute to motor neuron (MN) injury. It has emerged that certain aspects of ALS are non-cell-autonomous and that other cell types within the spinal cord, and peripheral immune system, contribute to the progression of the disease. However, due to the multifaceted and multisystemic nature of the disease, several pathological aspects are still to be clarified.
In this Special Issue of Cells, I invite you to contribute in the form of original research articles, reviews, or shorter perspective articles on all aspects related to the theme of molecular mechanisms and targets that might spread out the therapeutic perspective in ALS. Expert articles describing ALS mechanistic, functional, cellular, biochemical, or general aspects are highly welcome.
Dr. Giovanni Nardo
Manuscript Submission Information
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.
- amyotrophic lateral sclerosis
- molecular mechanisms, in vivo and in vitro models
- preclinical treatments
- therapeutic targets
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Title: Characterization of a novel long non-coding RNA in the antisense direction of SOD1 gene
Authors: Camilla Bernardini
Affiliation: Istituto di Anatomia Umana e Biologia Cellulare, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Title: How Protein Quality Control Mechanism Can Serve as a Therapeutics Strategy Against the Pathomechanism of Amyotrophic Lateral Sclerosis Neurodegeneration
Authors: Yuvraj Anandrao Jagtap; Prashant Kumar; Ankur Rakesh Dubey; Sumit Kinger; Akash Choudhary; Amit Mishra*
Affiliation: Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, 342037, Rajasthan, India
Title: Vascularisation of the motorcortex as a target for the development of new prevention and therapy strategies in ALS
Authors: Stefanie Schreiber
Affiliation: Helen Wills Neuroscience Institute, 132 Barker Hall, Mail Code 3190, University of California, Berkeley, CA 94720
Abstract: In ALS, vascular brain health seems to be of pivotal importance for protection from disease and slowing of the disease course. Indeed, ALS patients commonly suffer from cerebrovascular disease, vascular risk and cerebral small vessel alterations. Subsequent restricted vascular brain health exerts its detrimental effects on motoneurons through impaired endothelial cell formation caused by VEGF lowering, which in turn promotes blood-brain barrier leaks and inflammation. Reduced pericyte coverage further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview about the mechanistic underpinnings of impaired vascular brain health in ALS giving a roadmap how cutting-edge magnetic resonance imaging can help for its detection. We discuss fingerprints of motorcortex supply through more or less branches from the anterior and middle cerebral artery as a marker of vascular resistance and resilience against downstream effects of vascular risk and events in ALS. We further outline how certain lifestyle modifications adapted to the patients’ needs and capabilities have the potential to mechanistically target the brain’s microvasculature and in that advertise for rethinking ALS clinical trials and management.
Title: Pathological insights from different Amyotrophic Lateral Sclerosis animal models
Authors: Longhong Zhu, Shihua Li, Xiao-Jiang Li* and Peng Yin*
Affiliation: Guangdong Key Laboratory of Non-human Primate Research, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.
Title: Mutations in SLC22A5 and DHTKD1 genes may lead to ALS by affecting mitochondrial metabolism
Authors: Giuseppe ARENA
Affiliation: Luxembourg Centre for Systems Biomedicine (LCSB); UNIVERSITY OF LUXEMBOURG CAMPUS BELVAL; 6, Avenue du Swing; L-4367 Esch-sur-Alzette
Title: Correcting mitochondrial dysdynamism in ALS
Authors: Gerald W Dorn II
Affiliation: Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA
Title: Regulation of innate immune dysfunction as a therpy for ALS
Authors: Michael S. McGrath
Affiliation: Department of Medicine Suite 207, Bldg 3, ZSFG. 1001 Potrero Ave. San Francisco, CA. 94110 650-347-1258
Title: Towards the characterization of TDP-43 functional role(s) in cellular models exposed to ALS-related stress
Authors: Manuel Portero-Otin
Affiliation: Instituto de Investigación Biomédica de Lleida Fundación Dr. Pifarré, Lleida, Spain
Abstract: Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disease without disease-modifying treatments. Despite its clinical and pathophysiological heterogeneity, transactive response DNA-binding protein of 43 kDa (TDP-43) could link some of the disease hallmarks including impairment of RNA, protein and energetic homeostasis and oxidative stress. In this work, we hypothesized that dysregulation in TDP-43, can be modelled in cellular systems, leading to changes in sensitivity in front of ALS-related stress stimuli. We exposed the human cell line HeLa expressing an inducible silencing system to knock down the expression of TDP-43 to energetic and proteostasis stress and evaluated the effects on essential traits of cell homeostasis, including cell viability, oxygen consumption, and cell death. Results indicate TDP-43-dependent differences in basal cell metabolism, oxygen consumption and viability, but also in response to proteasome inhibitors and oxidative stress. In addition, HeLa cells were susceptible to the loss of function of TDP-43. We could not specify a single cell death mechanism since we found evidence supporting different pathways simultaneously. All in all, these results highlight the relevance of TDP-43 for maintaining cellular homeostasis and the use of proposed cellular models as a platform for screening relevant pathogenic pathways related to ALS and possible therapeutic targets.
Title: Biofluid biomarkers in amyotrophic lateral sclerosis prognosis: a review of recent developments and their applications in therapeutic translation
Authors: Daniel Sánchez-Tejerina1,2, Arnau Llauradó 1,2, Javier Sotoca 1,2, Verónica Lopez-Diego 1,2, María Salvadó 1,2, JM Vidal-Taboada 2, Raúl Juntas 1,2
Affiliation: 1. Neuromuscular Diseases Unit, European Reference Network on Rare Neuromuscular Diseases (ERN EURO-NMD), Neurology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute, European Reference Network for Neuromuscular and Rare Diseases EURO-NMD, 08035 Barcelona, Spain 2. Peripheral Nervous System Research Group. Vall d´Hebron Research Institut (VHIR). 08035 Barcelona, Spain
Title: Aggregation propensity does not predict neurotoxicity of pathogenic mutations in the ubiquitin adaptor protein, UBQLN2
Authors: Nathaniel Safren1,3*, Elizabeth Thuy Dao2, Harihar Miligunar Mohan3, Camellia Huang3, Bryce Trotter3, Carlos Castañeda2, Hank Paulson3,4, Sami Barmada3, Lisa M Sharkey3,4 *
Affiliation: 1. Present address: Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 2. Departments of Biology and Chemistry, Syracuse University, Syracuse, NY 13244 3. Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200 4. Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109-2200
Abstract: The ubiquitin-adaptor protein UBQLN2 promotes degradation of multiple aggregate-prone proteins implicated in neurodegenerative diseases including huntingtin, tau and a-synuclein. Missense mutations in UBQLN2 are also known to directly cause neurodegenerative disease along the ALS/FTD spectrum. Previously we demonstrated that the properties of UBQLN2 liquid-like molecular assemblies are altered by a specific pathogenic mutation, P506T, and that UBQLN2 aggregation propensity correlated with neurotoxicity. Building on this work, here we systematically assess the effects of multiple, spatially separated ALS-linked missense mutations on the properties of UBQLN2. We measured the effects of UBQLN2 mutants A282V, M446R, P497S, P479H and P506T on aggregation propensity, neurotoxicity, phase separation, autophagic flux and ability to regulate levels of a known protein substrate. Unlike the P506T mutation, other tested UBQLN2-ALS mutants did not reveal a predictable correlation between aggregation propensity and neurotoxicity. These results emphasize that the mechanism by which pathogenic UBQLN2 mutations cause neurodegeneration is likely complex and not necessarily tied to aggregation propensity of the mutant protein.
Title: Genetic down regulation of the mglu5 receptor dampens the reactive and neurotoxic phenotype of spinal cord astrocytes cultured from late symptomatic SOD1G93A mice
Authors: Carola Torazza 1, Francesca Provenzano 1, Matilde Balbi 1, Maria Cerminara2, Tiziana Bonifacino 1,3, Elena Gallia 1, Arianna Roberta Zerbo 1, Silvia Ravera 4, Cesare Usai 5, Paolo Scudieri 2, Aldamari
Affiliation: 1 Department of Pharmacy (DIFAR), University of Genoa, Viale Cembrano 4, 16148 Genova, Italy; 2 Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Largo Paolo Daneo, 316132 Genoa, Italy; 3 Inter-University Center for the Promotion of the 3Rs Principles in Teaching & Research (Centro 3R), Pisa, 56122, Italy; 4 Department of Experimental Medicine (DIMES), University of Genoa, Via Alberti L.B. 2, 16132 Genova, Italy; 5 Institute of Biophysics, National Research Council (CNR), Via De Marini 6, 16149 Genoa, Italy; 6 UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, Genoa, Italy; 7 Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute, KU Leuven - University of Leuven, Leuven, 3000, Belgium. 8 VIB-Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, 3000, Belgium. 9 Ionis Pharmaceuticals, Carlsbad, California, USA. 10 IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy;
Title: ALS associated change in circular RNA and RNA editing
Authors: Takashi Hosaka
Affiliation: Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan University of Tsukuba Hospital/Jichi Medical University Joint Ibaraki Western Regional Clinical Education Center, Chikusei, Ibaraki, 308-0813, Japan