Mutations in X-linked gene methyl-CpG-binding protein 2 (MECP2), a key transcriptional regulator, account for most cases of Rett syndrome (RTT), a devastating neurodevelopmental disorder with no known cure. Despite extensive research to elucidate MeCP2 functions, the mechanisms underlying RTT pathophysiology are still unclear. In addition to a variety of neurological symptoms, RTT also includes a plethora of additional phenotypical features including altered lipid metabolism, redox imbalance, immune dysfunction and mitochondrial abnormalities that explain its multisystemic nature. Here, we provide an overview of the current knowledge on the potential role of dysregulated inflammatory and immune responses in RTT. The findings show that abnormalities of humoral and cell-mediated immunity together with chronic low-grade inflammation in multiple organs represent not only clinical manifestations of RTT but rather can contribute to its development and deteriorating course. A future research challenge could be to target therapeutically immune dysfunction as a novel means for RTT management.

Compromised immune/inflammatory responses in Rett syndrome

Pecorelli A.
Primo
;
Cervellati C.
Secondo
;
Cordone V.;Valacchi G.
Ultimo
2020

Abstract

Mutations in X-linked gene methyl-CpG-binding protein 2 (MECP2), a key transcriptional regulator, account for most cases of Rett syndrome (RTT), a devastating neurodevelopmental disorder with no known cure. Despite extensive research to elucidate MeCP2 functions, the mechanisms underlying RTT pathophysiology are still unclear. In addition to a variety of neurological symptoms, RTT also includes a plethora of additional phenotypical features including altered lipid metabolism, redox imbalance, immune dysfunction and mitochondrial abnormalities that explain its multisystemic nature. Here, we provide an overview of the current knowledge on the potential role of dysregulated inflammatory and immune responses in RTT. The findings show that abnormalities of humoral and cell-mediated immunity together with chronic low-grade inflammation in multiple organs represent not only clinical manifestations of RTT but rather can contribute to its development and deteriorating course. A future research challenge could be to target therapeutically immune dysfunction as a novel means for RTT management.
2020
Pecorelli, A.; Cervellati, C.; Cordone, V.; Hayek, J.; Valacchi, G.
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0891584920302872-main.pdf

solo gestori archivio

Descrizione: versione editoriale
Tipologia: Full text (versione editoriale)
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 647.91 kB
Formato Adobe PDF
647.91 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
AAM.freeradbiomed.2020.02.023.pdf

accesso aperto

Descrizione: post print
Tipologia: Post-print
Licenza: Creative commons
Dimensione 4.07 MB
Formato Adobe PDF
4.07 MB Adobe PDF Visualizza/Apri

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2422509
Citazioni
  • ???jsp.display-item.citation.pmc??? 13
  • Scopus 29
  • ???jsp.display-item.citation.isi??? 26
social impact