Nogo-A and Nogo-66 receptor in amyotrophic lateral sclerosis.
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.
Teng
Felicia Yu Hsuan
FY
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Tang
Bor Luen
BL
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
D009185:Myelin Proteins; D000070798:Nogo Proteins; D020033:Protein Isoforms; C000603199:RTN4 protein, human; D020800:Receptor, Nerve Growth Factor; C000603201:Rtn4 protein, mouse