Primary progressive multiple sclerosis (PP-MS) is a less common progressive form of MS in approximately 10% of patients that manifest increasingly neurological disability from disease onset. To date, there are no approved treatments for the progressive stage. Therefore, identifying new therapeutic targets could open a new opportunity for PP-MS management. Several lines of evidence suggest the critical role of the Wnt/β-catenin pathway in immune-mediated diseases, like MS. This study was aimed to investigate whether aberrant expression of β-catenin is involved in PP-MS progression. By western blot analysis the expression of β-catenin was evaluated in CD4+ cells purified from peripheral blood of PP-MS patients. Specifically, nuclear expression of β-catenin was detected in CD4+ T cells purified from peripheral blood lymphocytes of PP-MS, and not of other neuromuscular diseases. In addition, no relevant expression of Wnt-1 was found in PP-MS patients, suggesting that the increase in nuclear β-catenin expression in these cells could be independent from canonical Wnt pathway. Taken together, our observations demonstrate that the deregulation of the β-catenin expression is involved in CD4+ T cells of PP-MS patients. Therefore, inhibitors of β-catenin pathway could be proposed as a promising candidate strategy for PP-MS cure.
Aberrant expression of β-catenin in CD4+ T cells isolated from primary progressive multiple sclerosis patients
BERESHCHENKO, OXANA;BRUSCOLI, STEFANO;RICCARDI, Carlo;
2017
Abstract
Primary progressive multiple sclerosis (PP-MS) is a less common progressive form of MS in approximately 10% of patients that manifest increasingly neurological disability from disease onset. To date, there are no approved treatments for the progressive stage. Therefore, identifying new therapeutic targets could open a new opportunity for PP-MS management. Several lines of evidence suggest the critical role of the Wnt/β-catenin pathway in immune-mediated diseases, like MS. This study was aimed to investigate whether aberrant expression of β-catenin is involved in PP-MS progression. By western blot analysis the expression of β-catenin was evaluated in CD4+ cells purified from peripheral blood of PP-MS patients. Specifically, nuclear expression of β-catenin was detected in CD4+ T cells purified from peripheral blood lymphocytes of PP-MS, and not of other neuromuscular diseases. In addition, no relevant expression of Wnt-1 was found in PP-MS patients, suggesting that the increase in nuclear β-catenin expression in these cells could be independent from canonical Wnt pathway. Taken together, our observations demonstrate that the deregulation of the β-catenin expression is involved in CD4+ T cells of PP-MS patients. Therefore, inhibitors of β-catenin pathway could be proposed as a promising candidate strategy for PP-MS cure.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
