Amyotrophic Lateral Sclerosis: Current Therapeutic Perspectives

Kumar, Vijay; Kashav, Tara; Hassan, Md. Imtaiyaz

doi:10.1007/978-981-13-0944-1_19

Cited by 5 publications

(7 citation statements)

References 196 publications

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“…Sporadic ALS cases account for approximately 90% of all patients and do not have an obvious genetic cause. Familial ALS accounts for the remaining 10% of patients and has been linked to mutations in genes such as Cu, Zn-superoxide dismutase 1 (SOD1), chromosome 9 open reading frame 72 (C9orf72), fused in sarcoma, and TAR DNA-binding protein 43 (TDP-43) [2]. Although ALS is classified as a rare disease, with a prevalence of 5 in 100,000 people living in the United States, the effects of the disease are calamitous for those who are afflicted [1].…”

Section: Introductionmentioning

confidence: 99%

“…Currently, only two drugs, Riluzole and Edaravone, have been approved by the U.S. Food and Drug Administration (FDA) to treat ALS. Riluzole is administered orally, only has a modest effect on slowing disease progression, and shows an extension of life of only a few months [2]. Edaravone has been shown to delay disease progression by only 33% when compared to a placebo, is costly, and must be administered intravenously [28].…”

Section: Introductionmentioning

confidence: 99%

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Protocatechuic Acid Extends Survival, Improves Motor Function, Diminishes Gliosis, and Sustains Neuromuscular Junctions in the hSOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

et al. 2020

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Amyotrophic lateral sclerosis (ALS) is a devastating disorder characterized by motor neuron apoptosis and subsequent skeletal muscle atrophy caused by oxidative and nitrosative stress, mitochondrial dysfunction, and neuroinflammation. Anthocyanins are polyphenolic compounds found in berries that possess neuroprotective and anti-inflammatory properties. Protocatechuic acid (PCA) is a phenolic acid metabolite of the parent anthocyanin, kuromanin, found in blackberries and bilberries. We explored the therapeutic effects of PCA in a transgenic mouse model of ALS that expresses mutant human Cu, Zn-superoxide dismutase 1 with a glycine to alanine substitution at position 93. These mice display skeletal muscle atrophy, hindlimb weakness, and weight loss. Disease onset occurs at approximately 90 days old and end stage is reached at approximately 120 days old. Daily treatment with PCA (100 mg/kg) by oral gavage beginning at disease onset significantly extended survival (121 days old in untreated vs. 133 days old in PCA-treated) and preserved skeletal muscle strength and endurance as assessed by grip strength testing and rotarod performance. Furthermore, PCA reduced astrogliosis and microgliosis in spinal cord, protected spinal motor neurons from apoptosis, and maintained neuromuscular junction integrity in transgenic mice. PCA lengthens survival, lessens the severity of pathological symptoms, and slows disease progression in this mouse model of ALS. Given its significant preclinical therapeutic effects, PCA should be further investigated as a treatment option for patients with ALS.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protocatechuic Acid Extends Survival, Improves Motor Function, Diminishes Gliosis, and Sustains Neuromuscular Junctions in the hSOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

et al. 2020

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“…There are various hypothesis explaining the AD pathogenesis; namely, cholinergic and amyloid hypothesis. Another hypothesis, tau hypothesis, is gaining popularity of which neurofibrillary tangles (NFTs) are the key players that are formed from hyperphosphorylated tau 19–22 . Some researchers are also focusing on metal ion hypothesis which states that imbalance of metal ions in the brain is associated to the onset and progression of AD.…”

Section: Introductionmentioning

confidence: 99%

Investigating binding mechanism of thymoquinone to human transferrin, targeting Alzheimer's disease therapy

Xue

DasGupta

Alam

et al. 2022

J of Cellular Biochemistry

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Iron deposition in the central nervous system (CNS) is one of the causes of neurodegenerative diseases. Human transferrin (hTf) acts as an iron carrier present in the blood plasma, preventing it from contributing to redox reactions. Plant compounds and their derivatives are frequently being used in preventing or delaying Alzheimer's disease (AD). Thymoquinone (TQ), a natural product has gained popularity because of its broad therapeutic applications. TQ is one of the significant phytoconstituent of Nigella sativa. The binding of TQ to hTf was determined by spectroscopic methods and isothermal titration calorimetry. We have observed that TQ strongly binds to hTf with a binding constant (K) of 0.22 × 106 M−1 and forming a stable complex. In addition, isothermal titration calorimetry revealed the spontaneous binding of TQ with hTf. Molecular docking analysis showed key residues of the hTf that were involved in the binding to TQ. We further performed a 250 ns molecular dynamics simulation which deciphered the dynamics and stability of the hTf‐TQ complex. Structure analysis suggested that the binding of TQ doesn't cause any significant alterations in the hTf structure during the course of simulation and a stable complex is formed. Altogether, we have elucidated the mechanism of binding of TQ with hTf, which can be further implicated in the development of a novel strategy for AD therapy.

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“…Japan-based company Fujifilm is working on Phase III clinical trials of Favipiravir in Japan and initiated Phase II trials in the US [ 54 ]. Other therapeutic approaches are discussed in other communications [ 5 , [55] , [56] , [57] , [58] , [59] , [60] ].…”

Section: Introductionmentioning

confidence: 99%

Evolutionary artificial intelligence based peptide discoveries for effective Covid-19 therapeutics

Kabra

Singh

2021

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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An epidemic caused by COVID-19 in China turned into pandemic within a short duration affecting countries worldwide. Researchers and companies around the world are working on all the possible strategies to develop a curative or preventive strategy for the same, which includes vaccine development, drug repurposing, plasma therapy, and drug discovery based on Artificial intelligence. Therapeutic approaches based on Computational biology and Machine-learning algorithms are specially considered, with a view that these could provide a fast and accurate outcome in the present scenario. As an effort towards developing possible therapeutics for COVID-19, we have used machine-learning algorithms for the generation of alignment kernels from diverse viral sequences of Covid-19 reported from India, China, Italy and USA. Using these diverse sequences we have identified the conserved motifs and subsequently a peptide library was designed against them. Of these, 4 peptides have shown strong binding affinity against the main protease of SARS-CoV-2 (M pro ) and also maintained their stability and specificity under physiological conditions as observed through MD Simulations. Our data suggest that these evolutionary peptides against COVID-19 if found effective may provide cross-protection against diverse Covid-19 variants.

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Amyotrophic Lateral Sclerosis: Current Therapeutic Perspectives

Cited by 5 publications

References 196 publications

Protocatechuic Acid Extends Survival, Improves Motor Function, Diminishes Gliosis, and Sustains Neuromuscular Junctions in the hSOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

Protocatechuic Acid Extends Survival, Improves Motor Function, Diminishes Gliosis, and Sustains Neuromuscular Junctions in the hSOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

Investigating binding mechanism of thymoquinone to human transferrin, targeting Alzheimer's disease therapy

Evolutionary artificial intelligence based peptide discoveries for effective Covid-19 therapeutics

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