Oxidative Stress As a Therapeutic Target in Amyotrophic Lateral Sclerosis: Opportunities and Limitations

Overview

Journal Diagnostics (Basel)

Specialty Radiology

Date 2021 Sep 28

PMID 34573888

Citations 13

Authors

Hee Ra Park

Eun Jin Yang

Affiliations

Soon will be listed here.

Abstract

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) and Lou Gehrig's disease, is characterized by a loss of the lower motor neurons in the spinal cord and the upper motor neurons in the cerebral cortex. Due to the complex and multifactorial nature of the various risk factors and mechanisms that are related to motor neuronal degeneration, the pathological mechanisms of ALS are not fully understood. Oxidative stress is one of the known causes of ALS pathogenesis. This has been observed in patients as well as in cellular and animal models, and is known to induce mitochondrial dysfunction and the loss of motor neurons. Numerous therapeutic agents have been developed to inhibit oxidative stress and neuroinflammation. In this review, we describe the role of oxidative stress in ALS pathogenesis, and discuss several anti-inflammatory and anti-oxidative agents as potential therapeutics for ALS. Although oxidative stress and antioxidant fields are meaningful approaches to delay disease progression and prolong the survival in ALS, it is necessary to investigate various animal models or humans with different subtypes of sporadic and familial ALS.

Citing Articles

Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer's, Parkinson's, and ALS.

Toader C, Tataru C, Munteanu O, Serban M, Covache-Busuioc R, Ciurea A Int J Mol Sci. 2024; 25(23.

PMID: 39684324 PMC: 11641752. DOI: 10.3390/ijms252312613.

Neuroprotective Effects of Olive Oil: A Comprehensive Review of Antioxidant Properties.

Goncalves M, Vale N, Silva P Antioxidants (Basel). 2024; 13(7).

PMID: 39061831 PMC: 11274152. DOI: 10.3390/antiox13070762.

Therapeutic targeting of ALS pathways: Refocusing an incomplete picture.

Maragakis N, de Carvalho M, Weiss M Ann Clin Transl Neurol. 2023; 10(11):1948-1971.

PMID: 37641443 PMC: 10647018. DOI: 10.1002/acn3.51887.

Reversing Dysdynamism to Interrupt Mitochondrial Degeneration in Amyotrophic Lateral Sclerosis.

Dorn 2nd G Cells. 2023; 12(8).

PMID: 37190097 PMC: 10136928. DOI: 10.3390/cells12081188.

Cellular Compartmentalization, Glutathione Transport and Its Relevance in Some Pathologies.

Vazquez-Meza H, Vilchis-Landeros M, Vazquez-Carrada M, Uribe-Ramirez D, Matuz-Mares D Antioxidants (Basel). 2023; 12(4).

PMID: 37107209 PMC: 10135322. DOI: 10.3390/antiox12040834.

References

Truzzi F, Tibaldi C, Zhang Y, Dinelli G, D Amen E . An Overview on Dietary Polyphenols and Their Biopharmaceutical Classification System (BCS). Int J Mol Sci. 2021; 22(11). PMC: 8197262. DOI: 10.3390/ijms22115514. View

Miranda-Lourenco C, Ribeiro-Rodrigues L, Fonseca-Gomes J, Tanqueiro S, Belo R, Ferreira C . Challenges of BDNF-based therapies: From common to rare diseases. Pharmacol Res. 2020; 162:105281. DOI: 10.1016/j.phrs.2020.105281. View

Dewil M, dela Cruz V, Van Den Bosch L, Robberecht W . Inhibition of p38 mitogen activated protein kinase activation and mutant SOD1(G93A)-induced motor neuron death. Neurobiol Dis. 2007; 26(2):332-41. DOI: 10.1016/j.nbd.2006.12.023. View

Smith R, Henry Y, Mattson M, Appel S . Presence of 4-hydroxynonenal in cerebrospinal fluid of patients with sporadic amyotrophic lateral sclerosis. Ann Neurol. 1998; 44(4):696-9. DOI: 10.1002/ana.410440419. View

Abe K, Pan L, Watanabe M, Kato T, Itoyama Y . Induction of nitrotyrosine-like immunoreactivity in the lower motor neuron of amyotrophic lateral sclerosis. Neurosci Lett. 1995; 199(2):152-4. DOI: 10.1016/0304-3940(95)12039-7. View

Ahmed T, Zulfiqar A, Arguelles S, Rasekhian M, Nabavi S, Sanches Silva A . Map kinase signaling as therapeutic target for neurodegeneration. Pharmacol Res. 2020; 160:105090. DOI: 10.1016/j.phrs.2020.105090. View

Zhang L, Guo Y, Wang H, Zhao L, Ma Z, Li T . Edaravone reduces Aβ-induced oxidative damage in SH-SY5Y cells by activating the Nrf2/ARE signaling pathway. Life Sci. 2019; 221:259-266. DOI: 10.1016/j.lfs.2019.02.025. View

Gibbs K, Kalmar B, Rhymes E, Fellows A, Ahmed M, Whiting P . Inhibiting p38 MAPK alpha rescues axonal retrograde transport defects in a mouse model of ALS. Cell Death Dis. 2018; 9(6):596. PMC: 5964181. DOI: 10.1038/s41419-018-0624-8. View

Rouleau G, CLARK A, Rooke K, Pramatarova A, Krizus A, Suchowersky O . SOD1 mutation is associated with accumulation of neurofilaments in amyotrophic lateral sclerosis. Ann Neurol. 1996; 39(1):128-31. DOI: 10.1002/ana.410390119. View

10.

Freedman D, Kuncl R, Weinstein S, Malila N, Virtamo J, Albanes D . Vitamin E serum levels and controlled supplementation and risk of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013; 14(4):246-51. PMC: 3673294. DOI: 10.3109/21678421.2012.745570. View

11.

Agar J, Durham H . Relevance of oxidative injury in the pathogenesis of motor neuron diseases. Amyotroph Lateral Scler Other Motor Neuron Disord. 2004; 4(4):232-42. DOI: 10.1080/14660820310011278. View

12.

Ferraro P, Cabona C, Meo G, Rolla-Bigliani C, Castellan L, Pardini M . Age at symptom onset influences cortical thinning distribution and survival in amyotrophic lateral sclerosis. Neuroradiology. 2021; 63(9):1481-1487. DOI: 10.1007/s00234-021-02681-3. View

13.

Bhinge A, Namboori S, Zhang X, VanDongen A, Stanton L . Genetic Correction of SOD1 Mutant iPSCs Reveals ERK and JNK Activated AP1 as a Driver of Neurodegeneration in Amyotrophic Lateral Sclerosis. Stem Cell Reports. 2017; 8(4):856-869. PMC: 5390134. DOI: 10.1016/j.stemcr.2017.02.019. View

14.

Fang T, Al Khleifat A, Meurgey J, Jones A, Leigh P, Bensimon G . Stage at which riluzole treatment prolongs survival in patients with amyotrophic lateral sclerosis: a retrospective analysis of data from a dose-ranging study. Lancet Neurol. 2018; 17(5):416-422. PMC: 5899963. DOI: 10.1016/S1474-4422(18)30054-1. View

15.

Kefalakes E, Boselt S, Sarikidi A, Ettcheto M, Bursch F, Naujock M . Characterizing the multiple roles of FGF-2 in SOD1 ALS mice in vivo and in vitro. J Cell Physiol. 2018; 234(5):7395-7410. DOI: 10.1002/jcp.27498. View

16.

Kirby J, Halligan E, Baptista M, Allen S, Heath P, Holden H . Mutant SOD1 alters the motor neuronal transcriptome: implications for familial ALS. Brain. 2005; 128(Pt 7):1686-706. DOI: 10.1093/brain/awh503. View

17.

Ohta Y, Yamashita T, Nomura E, Hishikawa N, Ikegami K, Osakada Y . Improvement of a decreased anti-oxidative activity by edaravone in amyotrophic lateral sclerosis patients. J Neurol Sci. 2020; 415:116906. DOI: 10.1016/j.jns.2020.116906. View

18.

Harraz M, Marden J, Zhou W, Zhang Y, Williams A, Sharov V . SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model. J Clin Invest. 2008; 118(2):659-70. PMC: 2213375. DOI: 10.1172/JCI34060. View

19.

Ohta Y, Nomura E, Shang J, Feng T, Huang Y, Liu X . Enhanced oxidative stress and the treatment by edaravone in mice model of amyotrophic lateral sclerosis. J Neurosci Res. 2018; 97(5):607-619. DOI: 10.1002/jnr.24368. View

20.

Blasco H, Garcon G, Patin F, Veyrat-Durebex C, Boyer J, Devos D . Panel of Oxidative Stress and Inflammatory Biomarkers in ALS: A Pilot Study. Can J Neurol Sci. 2016; 44(1):90-95. DOI: 10.1017/cjn.2016.284. View