Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a rapidly debilitating fatal neurodegenerative disorder, causing muscle atrophy and weakness, which leads to paralysis and eventual death. ALS has a multifaceted nature affected by many pathological mechanisms, including oxidative stress (also via protein aggre...
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/5/2400 |
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| author | Belgin Sever Halilibrahim Ciftci Hasan DeMirci Hilal Sever Firdevs Ocak Burak Yulug Hiroshi Tateishi Takahisa Tateishi Masami Otsuka Mikako Fujita Ayşe Nazlı Başak |
| author_facet | Belgin Sever Halilibrahim Ciftci Hasan DeMirci Hilal Sever Firdevs Ocak Burak Yulug Hiroshi Tateishi Takahisa Tateishi Masami Otsuka Mikako Fujita Ayşe Nazlı Başak |
| author_sort | Belgin Sever |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is a rapidly debilitating fatal neurodegenerative disorder, causing muscle atrophy and weakness, which leads to paralysis and eventual death. ALS has a multifaceted nature affected by many pathological mechanisms, including oxidative stress (also via protein aggregation), mitochondrial dysfunction, glutamate-induced excitotoxicity, apoptosis, neuroinflammation, axonal degeneration, skeletal muscle deterioration and viruses. This complexity is a major obstacle in defeating ALS. At present, riluzole and edaravone are the only drugs that have passed clinical trials for the treatment of ALS, notwithstanding that they showed modest benefits in a limited population of ALS. A dextromethorphan hydrobromide and quinidine sulfate combination was also approved to treat pseudobulbar affect (PBA) in the course of ALS. Globally, there is a struggle to prevent or alleviate the symptoms of this neurodegenerative disease, including implementation of antisense oligonucleotides (ASOs), induced pluripotent stem cells (iPSCs), CRISPR-9/Cas technique, non-invasive brain stimulation (NIBS) or ALS-on-a-chip technology. Additionally, researchers have synthesized and screened new compounds to be effective in ALS beyond the drug repurposing strategy. Despite all these efforts, ALS treatment is largely limited to palliative care, and there is a strong need for new therapeutics to be developed. This review focuses on and discusses which therapeutic strategies have been followed so far and what can be done in the future for the treatment of ALS. |
| first_indexed | 2024-03-09T20:38:34Z |
| format | Article |
| id | doaj.art-11a52e7a41e143b2a05727136283a33b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:38:34Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-11a52e7a41e143b2a05727136283a33b2023-11-23T23:03:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01235240010.3390/ijms23052400Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral SclerosisBelgin Sever0Halilibrahim Ciftci1Hasan DeMirci2Hilal Sever3Firdevs Ocak4Burak Yulug5Hiroshi Tateishi6Takahisa Tateishi7Masami Otsuka8Mikako Fujita9Ayşe Nazlı Başak10Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, TurkeyMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, JapanDepartment of Molecular Biology and Genetics, Koc University, Istanbul 34450, TurkeyMinistry of Health, Istanbul Training and Research Hospital, Physical Medicine and Rehabilitation Clinic, Istanbul 34098, TurkeyFaculty of Medicine, Kocaeli University, Kocaeli 41001, TurkeyDepartment of Neurology and Neuroscience, Faculty of Medicine, Alaaddin Keykubat University, Alanya 07425, TurkeyMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, JapanDivision of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, Fukuoka 830-0011, JapanMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, JapanMedicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, JapanSuna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (KUTTAM-NDAL), Koc University, Istanbul 34450, TurkeyAmyotrophic lateral sclerosis (ALS) is a rapidly debilitating fatal neurodegenerative disorder, causing muscle atrophy and weakness, which leads to paralysis and eventual death. ALS has a multifaceted nature affected by many pathological mechanisms, including oxidative stress (also via protein aggregation), mitochondrial dysfunction, glutamate-induced excitotoxicity, apoptosis, neuroinflammation, axonal degeneration, skeletal muscle deterioration and viruses. This complexity is a major obstacle in defeating ALS. At present, riluzole and edaravone are the only drugs that have passed clinical trials for the treatment of ALS, notwithstanding that they showed modest benefits in a limited population of ALS. A dextromethorphan hydrobromide and quinidine sulfate combination was also approved to treat pseudobulbar affect (PBA) in the course of ALS. Globally, there is a struggle to prevent or alleviate the symptoms of this neurodegenerative disease, including implementation of antisense oligonucleotides (ASOs), induced pluripotent stem cells (iPSCs), CRISPR-9/Cas technique, non-invasive brain stimulation (NIBS) or ALS-on-a-chip technology. Additionally, researchers have synthesized and screened new compounds to be effective in ALS beyond the drug repurposing strategy. Despite all these efforts, ALS treatment is largely limited to palliative care, and there is a strong need for new therapeutics to be developed. This review focuses on and discusses which therapeutic strategies have been followed so far and what can be done in the future for the treatment of ALS.https://www.mdpi.com/1422-0067/23/5/2400amyotrophic lateral sclerosis (ALS)oxidative stressprotein aggregationglutamate excitotoxicityapoptosisneuroinflammation |
| spellingShingle | Belgin Sever Halilibrahim Ciftci Hasan DeMirci Hilal Sever Firdevs Ocak Burak Yulug Hiroshi Tateishi Takahisa Tateishi Masami Otsuka Mikako Fujita Ayşe Nazlı Başak Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis International Journal of Molecular Sciences amyotrophic lateral sclerosis (ALS) oxidative stress protein aggregation glutamate excitotoxicity apoptosis neuroinflammation |
| title | Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis |
| title_full | Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis |
| title_fullStr | Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis |
| title_full_unstemmed | Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis |
| title_short | Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis |
| title_sort | comprehensive research on past and future therapeutic strategies devoted to treatment of amyotrophic lateral sclerosis |
| topic | amyotrophic lateral sclerosis (ALS) oxidative stress protein aggregation glutamate excitotoxicity apoptosis neuroinflammation |
| url | https://www.mdpi.com/1422-0067/23/5/2400 |
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