title: Therapeutic neuroprotective agents for amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal chronic neurodegenerative disease whose hallmark is proteinaceous, ubiquitinated, cytoplasmic inclusions in motor neurons and surrounding cells. Multiple mechanisms proposed as responsible for ALS pathogenesis include dysfunction of protein degradation, glutamate excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. It is therefore essential to gain a better understanding of the underlying disease etiology and search for neuroprotective agents that might delay disease onset, slow progression, prolong survival, and ultimately reduce the burden of disease. Because riluzole, the only Food and Drug Administration (FDA)-approved treatment, prolongs the ALS patient's life by only 3 months, new therapeutic agents are urgently needed. In this review, we focus on studies of various small pharmacological compounds targeting the proposed pathogenic mechanisms of ALS and discuss their impact on disease progression.
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Rachna S
authors.initials: RS
authors.lastname: Pandya
authors.forename: Haining
authors.initials: H
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Robert
authors.initials: R
authors.lastname: Bowser
authors.forename: Robert M
authors.initials: RM
authors.lastname: Friedlander
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D059748:Proteolysis; D019782:Riluzole / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D050505:Mutant Proteins; D018696:Neuroprotective Agents; D019782:Riluzole; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase