title: Neuroprotective agents target molecular mechanisms of disease in ALS.
abstract: Amyotrophic lateral sclerosis (ALS) is a debilitating disease characterized by progressive loss of voluntary motor neurons leading to muscle atrophy, weight loss and respiratory failure. Evidence suggests that inflammation, oxidative stress, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity and proteasomal dysfunction are all responsible for ALS pathogenesis. We review neuroprotective agents with the ability to reduce ALS-related bodyweight loss, summarize the various therapies tested on animal models targeting the proposed molecular mechanisms, compare their effects on bodyweight loss, muscle damage, disease onset, duration and survival, and analyze their structure-activity relationships, with the overall goal of creating a screening strategy for further clinical application.
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Fotinos
authors.affiliation: Aimcan Pharma Research & Technologies, 398 Laird Rd, Guelph, ON N1G 3X7, Canada.
authors.forename: Lilly L J
authors.initials: LL
authors.lastname: Mao
authors.affiliation: Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Nazem
authors.initials: N
authors.lastname: Atassi
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Zhou
authors.affiliation: Aimcan Pharma Research & Technologies, 398 Laird Rd, Guelph, ON N1G 3X7, Canada.
authors.forename: Sarfraz
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Department of Histology and Embryology, Weifang Medical University, Weifang, Shandong, China.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Berry
authors.affiliation: Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Merit E
authors.initials: ME
authors.lastname: Cudkowicz
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: xwang@rics.bwh.harvard.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009133:Muscular Atrophy / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D015431:Weight Loss / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents