Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis

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SEVER B., Ciftci H., DeMirci H., Sever H., Ocak F., Yulug B., ...Daha Fazla

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, cilt.23, sa.5, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 23 Sayı: 5
  • Basım Tarihi: 2022
  • Doi Numarası: 10.3390/ijms23052400
  • Dergi Adı: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: amyotrophic lateral sclerosis (ALS), oxidative stress, protein aggregation, glutamate excitotoxicity, apoptosis, neuroinflammation, axonal degeneration, edaravone, riluzole, induced pluripotent stem cells (iPSCs), PLACEBO-CONTROLLED TRIAL, NEURITE OUTGROWTH INHIBITOR, RANDOMIZED SEQUENTIAL TRIAL, HEAT-SHOCK PROTEINS, DOUBLE-BLIND, CLINICAL-TRIAL, MOUSE MODEL, DISEASE PROGRESSION, PROLONGS SURVIVAL, VALPROIC ACID
  • Anadolu Üniversitesi Adresli: Evet

Özet

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.