Open AccessNogo‐A and Nogo‐66 receptor in amyotrophic lateral sclerosis
Author(s) -
Teng Felicia Yu Hsuan,
Tang Bor Luen
Publication year - 2008
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00351.x
Subject(s) - amyotrophic lateral sclerosis , low affinity nerve growth factor receptor , gene isoform , denervation , neuroscience , motor neuron , receptor , disease , biology , microbiology and biotechnology , neurotrophin , medicine , pathology , endocrinology , gene , genetics , spinal cord
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.