Molecular and Cellular Mechanisms Affected in ALS

Gall, Laura Le; Anakor, Ekene; Connolly, Owen; Vijayakumar, Udaya Geetha; Duddy, William; Duguez, Stéphanie

doi:10.3390/jpm10030101

Cited by 86 publications

(87 citation statements)

References 325 publications

(442 reference statements)

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“…Several mutations in seemingly unrelated genes, e.g., superoxide dismutase 1 (SOD1), chromosome 9 open reading frame 72 (C9orf72), or TAR DNA-binding protein 43 (TARDBP), have been described and it remains possible that ALS is not a single disease entity but a conglomerate of different diseases with a similar clinical endpoint. In most patients, however, no recurrent mutations can be found and for these “sporadic” ALS cases, non-genetic factors might play a role [ 141 , 142 , 143 ].…”

Section: Herv-k In Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Endogenous Retroviruses in Nervous System Disorders

et al. 2021

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Human endogenous retroviruses (HERV) have been implicated in the pathogenesis of several nervous system disorders including multiple sclerosis and amyotrophic lateral sclerosis. The toxicity of HERV-derived RNAs and proteins for neuronal cells has been demonstrated. The involvement of HERV in the pathogenesis of currently incurable diseases might offer new treatment strategies based on the inhibition of HERV activities by small molecules or therapeutic antibodies.

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Section: Herv-k In Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Endogenous Retroviruses in Nervous System Disorders

et al. 2021

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“…Clinical diagnosis of ALS is difficult in the early period because the patients may not show any upper or lower motor neuron signs [ 10 ]. In addition ALS symptoms can be quite heterogeneous and show resemblance to many neurological diseases.…”

Section: Introductionmentioning

confidence: 99%

Bayesian Network as a Decision Tool for Predicting ALS Disease

et al. 2021

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Clinical diagnosis of amyotrophic lateral sclerosis (ALS) is difficult in the early period. But blood tests are less time consuming and low cost methods compared to other methods for the diagnosis. The ALS researchers have been used machine learning methods to predict the genetic architecture of disease. In this study we take advantages of Bayesian networks and machine learning methods to predict the ALS patients with blood plasma protein level and independent personal features. According to the comparison results, Bayesian Networks produced best results with accuracy (0.887), area under the curve (AUC) (0.970) and other comparison metrics. We confirmed that sex and age are effective variables on the ALS. In addition, we found that the probability of onset involvement in the ALS patients is very high. Also, a person’s other chronic or neurological diseases are associated with the ALS disease. Finally, we confirmed that the Parkin level may also have an effect on the ALS disease. While this protein is at very low levels in Parkinson’s patients, it is higher in the ALS patients than all control groups.

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“…Among them, TDP-43 , SOD1 , FUS/TLS , TARDBP , FIG4 and C9ORF72 are some genes whose mutations are strongly implicated in the development of the pathology [ 4 , 5 , 6 , 7 ]. These genes affect key cellular processes, including RNA metabolism, stress response and autophagy [ 8 ]. In particular, oxidative stress can induce the formation of stress granules, i.e., membraneless organelles composed of certain RNAs and proteins.…”

Section: Introductionmentioning

confidence: 99%

NMR Characterization of Angiogenin Variants and tRNAAla Products Impacting Aberrant Protein Oligomerization

Fagagnini

Garavís

Gómez‐Pinto

et al. 2021

IJMS

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Protein oligomerization is key to countless physiological processes, but also to abnormal amyloid conformations implicated in over 25 mortal human diseases. Human Angiogenin (h-ANG), a ribonuclease A family member, produces RNA fragments that regulate ribosome formation, the creation of new blood vessels and stress granule function. Too little h-ANG activity leads to abnormal protein oligomerization, resulting in Amyotrophic Lateral Sclerosis (ALS) or Parkinson’s disease. While a score of disease linked h-ANG mutants has been studied by X-ray diffraction, some elude crystallization. There is also a debate regarding the structure that RNA fragments adopt after cleavage by h-ANG. Here, to better understand the beginning of the process that leads to aberrant protein oligomerization, the solution secondary structure and residue-level dynamics of WT h-ANG and two mutants i.e., H13A and R121C, are characterized by multidimensional heteronuclear NMR spectroscopy under near-physiological conditions. All three variants are found to adopt well folded and highly rigid structures in the solution, although the elements of secondary structure are somewhat shorter than those observed in crystallography studies. R121C alters the environment of nearby residues only. By contrast, the mutation H13A affects local residues as well as nearby active site residues K40 and H114. The conformation characterization by CD and 1D 1H NMR spectroscopies of tRNAAla before and after h-ANG cleavage reveals a retention of the duplex structure and little or no G-quadruplex formation.

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Molecular and Cellular Mechanisms Affected in ALS

Cited by 86 publications

References 325 publications

Endogenous Retroviruses in Nervous System Disorders

Endogenous Retroviruses in Nervous System Disorders

Bayesian Network as a Decision Tool for Predicting ALS Disease

NMR Characterization of Angiogenin Variants and tRNAAla Products Impacting Aberrant Protein Oligomerization

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