Review Article
Volume 12 Issue 10 - 2020
Convergence in Motor Nerve Diseases: Relating ALS Etiology to Diagnosis in MND Mimics
Denis Larrivee1,2*
1Mind and Brain Institute, Loyola University Chicago, USA
2Arts and Sciences, University of Navarra Medical School, Spain
*Corresponding Author: Denis Larrivee, Mind and Brain Institute, Loyola University Chicago, USA and Arts and Sciences, University of Navarra Medical School, Spain.
Received: September 07, 2020; Published: September 19, 2020


Amyotrophic lateral sclerosis (ALS) is a progressive, paralytic disorder characterized by degeneration of motor neurons in the brain and spinal cord, with the eventual atrophy of most muscles, including those of the diaphragm. Among the motor nerve diseases (MNDs), ALS is the most common, amounting to 80% of cases, and has an overall prevalence of about 1 to 9 cases per 100,000 across the globe. Research into the etiological factors contributing to the disease has shown that multiple factors are causative for ALS, with three major domains of cellular processes - RNA and protein processing and homeostasis, cytoskeletal mechanics, and neuroinflammation - among the predominant factors discovered to date. Conversely, much less is known of the non-ALS MNDs, which variously mimic ALS symptoms, anatomical targeting and disease progression. Based on their resemblance and recent discoveries of shared causative mechanisms, knowledge of their etiology and degenerative events could benefit from ALS findings, which can be expected to be mutually beneficial for ALS diagnosis and therapy. Accordingly, this paper presents current genetic, mechanistic, and biomarker findings of shared dysfunctions of ALS and the non ALS MNDs, illustrating a number of converging mechanisms that could be targeted to assess prognosis and therapeutic intervention.

Keywords: Motor Nerve Diseases; Amyotrophic Lateral Sclerosis; Spinal Muscular Atrophy; ASC 1 Complex; Primary Lateral Sclerosis; Biomarkers; Neurofilament Protein


  1. Robert HB., et al. “Amyotrophic Lateral Sclerosis”. New England Journal of Medicine2 (2017): 162-172.
  2. Fen-Biao G., et al. “Dysregulated molecular pathways in amyotrophic lateral sclerosis-frontotemporal dementia spectrum disorder”. The EMBO Journal 36 (2017): 2931-2950.
  3. Yedavalli VS., et al. “Amyotrophic Lateral Sclerosis and its Mimics/Variants: A Comprehensive Review”. Journal of Clinical Imaging Science 8 (2018): 53.
  4. Binkai C., et al. “The neurodegenerative diseases ALS and SMA are linked at the molecular level via the ASC-1 complex”. Nucleic Acids Research22 (2018): 11939-11951.
  5. Benatar B., et al. “ALS biomarkers for therapy development: state of the field and future directions”. Muscle Nerve 53 (2016): 169-182.
  6. Finsterer J and Burgunder JM. “Recent progress in the genetics of motor neuron disease”. European Journal of Medical Genetics 57 (2014): 103e112.
  7. Pensato V., et al. “TUBA4A gene analysis in sporadic amyotrophic lateral sclerosis: identification of novel mutations”. Journal of Neurology 262 (2015): 1376-1378.
  8. Puls I., et al. “Mutant dynactin in motor neuron disease”. Nature Genetics 33 (2003): 455-456.
  9. Kuz ́ma-Kozakiewicz M., et al. “Dynactin deficiency in the cns of humans with sporadic ALS and mice with genetically determined motor neuron degeneration”. Neurochemistry Research 38 (2013): 2463-2473.
  10. Wu CH., et al. “Mutations in the profilin1 gene cause familial amyotrophic lateral sclerosis”. Nature 488 (2012): 499-503.
  11. Neumann M., et al. “Ubiquitinated TDP-43 in fronto-temporal lobar degeneration and amyotrophic lateral sclerosis”. Science 314 (2006): 130-133.
  12. Kwiatkowski TJ Jr., et al. “Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis”. Science 323 (2009): 1205-1208.
  13. DeJesus-Hernandez M., et al. “Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS”. Neuron 72 (2011): 245-256.
  14. Renton AE., et al. “A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD”. Neuron 72 (2011): 257-268.
  15. Rosen DR., et al. “Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis”. Nature 362 (1993): 59-62.
  16. Chen S., et al. “Genetics of amyotrophic lateral sclerosis: an update”. Molecular Neurodegeneration 8 (2013): 28.
  17. He J Zhang QJ., et al. “Molecular analysis of SMN1, SMN2, NAIP, GTF2H2, and H4F5 genes in 157 Chinese patients with spinal muscular atrophy”. Gene 518 (2013): 325e9.
  18. Fallini C., et al. “Dynamics of survival of motor neuron (SMN) protein interaction with the mRNA-binding protein IMP1 facilitates its trafficking into motor neuron axons”. Developmental Neurobiology (2013).
  19. Maiti D., et al. “Isolated exon 8 deletion in type 1 spinal muscular atrophy with bilateral optic atrophy: unusual genetic mutation leading to un- usual manifestation?” Journal of Postgraduate Medicine 58 (2012): 294e5.
  20. Branchu J., et al. “Shift from extracellular signal-regulated kinase to AKT/cAMP response element-binding protein pathway increases survival-motor-neuron expression in spinal- muscular-atrophy-like mice and patient cells”. Journal of Neuroscience 33 (2013): 4280e94.
  21. Boczonadi V., et al. “EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia”. Nature Communication 5 (2014): 4287.
  22. Evgrafov OV., et al. “Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy”. Nature Genetics 36 (2004): 602-606.
  23. Amornvit J., et al. “A novel p.T139M mutation in HSPB1 highlighting the phenotypic spectrum in a family”. Brain Behavior 7 (2017): e00774.
  24. Peeters K., et al. “Molecular Defects in the motor adaptor BICD2 cause proximal spinal muscular atrophy with autosomal-dominant inheritance”. American Journal of Human Genetics (2013).
  25. Minamiyama M., et al. “Naratriptan mitigates CGRP1-associated motor neuron degeneration caused by an expanded polyglutamine repeat tract”. Nature Medicine 18 (2012):1531e8.
  26. Chow CY., et al. “Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS”. American Journal of Human Genetics 84 (2009): 85e8.
  27. Figlewicz DA and Orrel RW. “The genetics of motor neuron diseases”. ALS 4 (2003): 225-231.
  28. Binkai C., et al. “The neurodegenerative diseases ALS and SMA are linked at the molecular level via the ASC-1 complex”. Nucleic Acids Research 22 (2018): 11939-11951.
  29. Darras BT., et al. “Neurofilament as a potential biomarker for spinal muscular atrophy”. Annals of Clinical and Translational Neurology 5 (2019): 932-944.
  30. Magri F., et al. “MiRNA in spinal muscular atrophy pathogenesis and therapy”. Journal of Cell and Molecular Medicine2 (2018): 755-767.
  31. Karen M., et al. “Beta-band intermuscular coherence: a novel biomarker of upper motor neuron dysfunction in motor neuron disease”. Brain 135 (2012): 2849-2864.
Citation: Denis Larrivee. “Convergence in Motor Nerve Diseases: Relating ALS Etiology to Diagnosis in MND Mimics”. EC Neurology 12.10 (2020): 26-36.

PubMed Indexed Article

EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005

EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777

EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347

EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478

EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253

EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033

EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992

EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505

EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793

EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211

EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047

EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560

EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318

EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819

EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840

EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344

EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476

EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658

EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489

EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278

EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108

EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571

EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333

EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883

EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001

EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937

EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723

EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726

EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603

EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646

EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616

EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290

EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226

EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812

EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268

News and Events

December Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the December issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

ECronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before December 17, 2021.

Certificate of Publication

ECronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

ECronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.

Immediate Assistance

The prime motto of this team is to clarify all the queries without any delay or hesitation to avoid the inconvenience. For immediate assistance on your queries please don't hesitate to drop an email to