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AIMS Neuroscience

2022, Volume 9, Issue 4: 423-443. doi: 10.3934/Neuroscience.2022023
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Biomarkers and molecular mechanisms of Amyotrophic Lateral Sclerosis

Running title:Running Title: ALS Detection and its Mechanism of Development
  • AllExcel, Inc. Shelton, CT, USA
  • Received: 03 July 2022 Revised: 29 October 2022 Accepted: 02 November 2022 Published: 10 November 2022

  • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in adults involving non-demyelinating motor disorders. About 90% of ALS cases are sporadic, while 10–12% of cases are due to some genetic reasons. Mutations in superoxide dismutase 1 (SOD1), TAR, c9orf72 (chromosome 9 open reading frame 72) and VAPB genes are commonly found in ALS patients. Therefore, the mechanism of ALS development involves oxidative stress, endoplasmic reticulum stress, glutamate excitotoxicity and aggregation of proteins, neuro-inflammation and defective RNA function. Cholesterol and LDL/HDL levels are also associated with ALS development. As a result, sterols could be a suitable biomarker for this ailment. The main mechanisms of ALS development are reticulum stress, neuroinflammation and RNA metabolism. The multi-nature development of ALS makes it more challenging to pinpoint a treatment.

    Citation: Ashok Chakraborty, Anil Diwan. Biomarkers and molecular mechanisms of Amyotrophic Lateral Sclerosis[J]. AIMS Neuroscience, 2022, 9(4): 423-443. doi: 10.3934/Neuroscience.2022023

    Related Papers:

  • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in adults involving non-demyelinating motor disorders. About 90% of ALS cases are sporadic, while 10–12% of cases are due to some genetic reasons. Mutations in superoxide dismutase 1 (SOD1), TAR, c9orf72 (chromosome 9 open reading frame 72) and VAPB genes are commonly found in ALS patients. Therefore, the mechanism of ALS development involves oxidative stress, endoplasmic reticulum stress, glutamate excitotoxicity and aggregation of proteins, neuro-inflammation and defective RNA function. Cholesterol and LDL/HDL levels are also associated with ALS development. As a result, sterols could be a suitable biomarker for this ailment. The main mechanisms of ALS development are reticulum stress, neuroinflammation and RNA metabolism. The multi-nature development of ALS makes it more challenging to pinpoint a treatment.

    Abbreviations

    AD

    Alzheimer's Disease

         Ataxin-2

    ATXN2 Gene-Product

         ALS

    Amyotrophic Lateral Sclerosis

         HSP

    Hereditary spastic paralysis

         AMPA

    α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

         LDL

    Low Density Lipoprotein

         AOA2

    Ataxia with Oculomotor Apraxia Type 2

         MMP-2

    Metalloproteinase-2

         fALS

    Familial ALS

         MMP-9

    Metalloproteinase-9

         sALS

    Sporadic ALS

         NfL

    Neurofilament Light Chain

         APOE

    Apolipoprotein E

         NMDA

    α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole-propionic Acid

         Ataxin-2

    ATXN2 Gene-Product

         PD

    Parkinson's Disease

         CCR2

    C-C Chemokine Receptor Type 2

         pNfH

    Phosphorylated Neurofilament Heavy Chain

         c9orf72

    Chromosome 9 Open Reading Frame 72

         Optn

    Optineurin

         CMT type 4 J

    Charcot-Marie-Tooth disease type 4

         OX40

    CD134 (TNFRSF4)

         CRP

    C-Reactive Protein

         PLS

    Primary lateral sclerosis

         CSF

    Cerebrospinal Fluid

         RBP

    RNA-binding protein

         DFT

    Frontotemporal Dementia

         RNA

    Ribonucleic acid

         ELISA

    Enzyme-Linked Immunosorbent Assay

         ROS

    Reactive Oxygen Species

         EMMPRIN

    Extracellular Matrix Metalloproteinase Inducer

         SCAR1

    Spinocerebellar Ataxia, Autosomal Recessive 1

         FDA

    U.S. Food and Drug Administration

         SMA

    Spinal muscular atrophy

         FIG 4

    FIG4 Phosphoinositide 5-Phosphatase

         SOD

    Superoxide Dismutase 1

         FTD

    Frontotemporal disorder

         TDP-43

    TAR DNA-Binding Protein 43

         FTLD

    Frontotemporal lobar degeneration

         TARDBP

    TAR DNA Binding Protein

         FUS

    Fused in Sarcoma

         TNF-α

    Tumor Necrosis Factor-α

         GM-CSF

    Granulocyte Macrophage Colony Stimulating Factor

         VAPB

    Vesicle-associated Membrane Protein-associated Protein B

         HDL

    High-density lipoprotein

         VCP

    Valosin Containing Protein

         HMGB1

    High Density Lipoprotein

         WASP

    Wiskott–Aldrich syndrome protein

         APOE

    Apolipoprotein E

         wr-CRP

    Wide Range C-Reactive Protein
    加载中

    Acknowledgments


    We acknowledge all our colleagues for their help during the preparation of the manuscript by providing all the relevant information. We are also thankful to Ms. Bethany Pond (Analytical Chemist at AllExcel, Inc.) for editing the manuscript.

    Funding


    This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

    Consent for publications


    Both the authors have agreed to submit this paper for publication.

    Ethical approval


    Not applicable.

    Conflict of interest


    The authors declare no conflict of interests.

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