Neprilysin participates in skeletal muscle regeneration and is accumulated in abnormal muscle fibres of inclusion body myositis.

Aldobrando Broccolini, Enzo Ricci, Massimiliano Mirabella, Teresa Gidaro, Roberta Morosetti, Carla Gliubizzi, Tiziana Servidei, Pietro Attilio Tonali, Mario Pescatori

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

35 Citazioni (Scopus)

Abstract

Neprilysin (NEP, EP24.11), a metallopeptidase originally shown to modulate signalling events by degrading small regulatory peptides, is also an amyloid-beta- (Abeta) degrading enzyme. We investigated a possible role of NEP in inclusion body myositis (IBM) and other acquired and hereditary muscle disorders and found that in all myopathies NEP expression was directly associated with the degree of muscle fibre regeneration. In IBM muscle, NEP protein was also strongly accumulated in Abeta-bearing abnormal fibres. In vitro, during the experimental differentiation of myoblasts, NEP protein expression was regulated at the post-transcriptional level with a rapid increase in the early stage of myoblast differentiation followed by a gradual reduction thereafter, coincident with the progression of the myogenic programme. Treatment of differentiating muscle cells with the NEP inhibitor dl-3-mercapto-2-benzylpropanoylglycine resulted in impaired differentiation that was mainly associated with an abnormal regulation of Akt activation. Therefore, NEP may play an important role during muscle cell differentiation, possibly through the regulation, either directly or indirectly, of the insulin-like growth factor I-driven myogenic programme. In IBM muscle increased NEP may be instrumental in (i) reducing the Abeta accumulation in vulnerable fibres and (ii) promoting a repair/regenerative attempt of muscle fibres possibly through the modulation of insulin-like growth factor I-dependent pathways.
Lingua originaleEnglish
pagine (da-a)777-789
Numero di pagine13
RivistaJournal of Neurochemistry
Stato di pubblicazionePubblicato - 2006

Keywords

  • Neprilysin
  • muscle fibres
  • myositis
  • skeletal muscle regeneration

Fingerprint Entra nei temi di ricerca di 'Neprilysin participates in skeletal muscle regeneration and is accumulated in abnormal muscle fibres of inclusion body myositis.'. Insieme formano una fingerprint unica.

Cita questo