A panel of macroautophagy markers in lymphomonocytes of patients with amyotrophic lateral sclerosis

• Published in: Amyotrophic lateral sclerosis 2012-01, Vol.13 (1), p.119-124
• Main Authors: Sala, Gessica, Tremolizzo, Lucio, Melchionda, Laura, Stefanoni, Giovanni, Derosa, Matteo, Susani, Emanuela, Pagani, Ambrogio, Perini, Michele, Pettini, Paola, Tavernelli, Fiorella, Zarcone, Davide, Ferrarese, Carlo
• Format: Article
• Language: English
• Subjects: Aged; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - blood; Amyotrophic Lateral Sclerosis - drug therapy; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Autophagy - physiology; Beclin-1; Biomarkers - blood; Cells, Cultured; Female; Humans; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - metabolism; lymphomonocytes; macroautophagy; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Middle Aged; Neuroprotective Agents - therapeutic use; Riluzole - therapeutic use
• ISSN: 1748-2968; 1471-180X
• DOI: 10.3109/17482968.2011.611139

Abstract A potential role for macroautophagy dysfunction in the pathogenesis of amyotrophic lateral sclerosis (ALS) was hypothesized after the demonstration that selected markers are up-regulated in post mortem samples obtained from both patients and animal models of disease. We hypothesized that a putative dysfunction of this catabolic pathway could be operative also in peripheral blood mononuclear cells (PBMC) obtained from ALS patients, since these cells represent an accessible model for studying molecular pathogenesis events in neuropsychiatric disorders. Beclin-1 and LC3II immunoreactivity were assessed in PBMC from 15 ALS patients and 15 controls by Western blot analysis. The expression of Atg12 mRNA was also assessed by real-time PCR. No significant difference was observed for all these parameters between patients and controls, although PBMC displayed a clear macroautophagy induction following exposure to rapamycin and lithium. Finally, we excluded a putative interference of riluzole demonstrating that LC3II immunoreactivity did not change in riluzole-treated SH-SY5Y neuroblastoma cells. In conclusion, the results of our pilot study do not support the idea of a systemic macroautophagic dysfunction in ALS, although they confirm that PBMC are a suitable peripheral marker for monitoring the effects of drugs interfering with this catabolic pathway.