title: Nogo-A and Nogo-66 receptor in amyotrophic lateral sclerosis.
abstract: Nogo/reticulon (RTN)-4 has been strongly implicated as a disease marker for the motor neuron disease amyotrophic lateral sclerosis (ALS). Nogo isoforms, including Nogo-A, are ectopically expressed in the skeletal muscle of ALS mouse models and patients and their levels correlate with the disease severity. The notion of a direct involvement of Nogo-A in ALS aetiology is supported by the findings that Nogo-A deletion in mice reduces muscle denervation and prolongs survival, whereas overexpression of Nogo-A destabilizes motor nerve terminals and promotes denervation. Another intriguing, and somewhat paradoxical, recent finding revealed that binding of the Nogo-66 receptor (NgR) by either agonistic or antagonistic Nogo-66-derived peptides protects against p75 neurotrophin receptor (p75(NTR))-dependent motor neuron death. Ligand binding by NgR could result in subsequent engagement of p75(NTR), and this association could preclude pro-apoptotic signalling by the latter. Understanding the intricate interplay among Nogo isoforms, NgR and p75(NTR) in ALS disease progression may provide important, therapeutically exploitable information.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Felicia Yu Hsuan
authors.initials: FY
authors.lastname: Teng
authors.forename: Bor Luen
authors.initials: BL
authors.lastname: Tang
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000818:Animals; D016923:Cell Death; D006801:Humans; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009185:Myelin Proteins / Q000378:metabolism*; D000070798:Nogo Proteins; D020033:Protein Isoforms / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism
chemical_list: D009185:Myelin Proteins; D000070798:Nogo Proteins; D020033:Protein Isoforms; C000603199:RTN4 protein, human; D020800:Receptor, Nerve Growth Factor; C000603201:Rtn4 protein, mouse