Increased expression of neutral endopeptidase (NEP) and aminopeptidase N (APN) on peripheral blood mononuclear cells in patients with multiple sclerosis

Improved clinical behavior of established relapsing-remitting experimental autoimmune encephalomyelitis following treatment with endogenous opioids: Implications for the treatment of multiple sclerosis

“…McLaughlin and Zagon, 2013;Campbell et al, 2012;Hammer et al, 2013) suggests that the underlying pathophysiology may be the same and share similar manifestations. Furthermore, it is known that the peptidases that break down enkephalins, and specifically neprilysin, are activated in patients with MS (Ziaber et al, 1999(Ziaber et al, , 2000. Whether the dysregulation of the OGF-OGFr axis involves increased enkephalinase activity (Gironi et al, 2000;Jankovic, 1991;Weir et al, 2006), as well as decreased processing of the precursor proenkephalin is unknown.…”

Endogenous Opioids Regulate Expression of Experimental Autoimmune Encephalomyelitis: A New Paradigm for the Treatment of Multiple Sclerosis

“…Proteases associated with degradation of opioid peptides are increased with MS. For example, Ziaber et al (48,49) reported an increase in CD10 (neutral endopeptidase-NEP, EC 3.4.24.11) and CD13 (aminopeptidase N, AP-N, EC 3.4.11.2) in MS patients during the course of exacerbation and chronic MS, but low expression of these molecules during remission. Because these ectoenzymes are enkephalin-degrading (50,51), this could depress the population of enkephalins related to the inhibition of cell proliferation.…”

Ectopeptidases in pathophysiology

“…(16± 18) In contrast, the loss of DPPIV and g-GT from the surface of lymphocytes is associated with acute and chronic T lymphocytic leukemic diseases. (19,20) Ectopeptidases also appear to be dysregulated in putative autoimmune diseases such as multiple sclerosis (21,22) and rheumatoid arthritis (23,24) as well as sarcoidosis (7) and HIV infection (6,25) ( Table 1).…”