title: A panel of macroautophagy markers in lymphomonocytes of patients with amyotrophic lateral sclerosis.
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.
authors.affiliation: Department of Neuroscience and Biomedical Technologies, University of Milano-Bicocca. via Cadore 48, Monza (MB), Italy. gessica.sala@unimib.it
authors.forename: Gessica
authors.initials: G
authors.lastname: Sala
authors.forename: Lucio
authors.initials: L
authors.lastname: Tremolizzo
authors.forename: Laura
authors.initials: L
authors.lastname: Melchionda
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stefanoni
authors.forename: Matteo
authors.initials: M
authors.lastname: Derosa
authors.forename: Emanuela
authors.initials: E
authors.lastname: Susani
authors.forename: Ambrogio
authors.initials: A
authors.lastname: Pagani
authors.forename: Michele
authors.initials: M
authors.lastname: Perini
authors.forename: Paola
authors.initials: P
authors.lastname: Pettini
authors.forename: Fiorella
authors.initials: F
authors.lastname: Tavernelli
authors.forename: Davide
authors.initials: D
authors.lastname: Zarcone
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrarese
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000188:drug therapy; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D015415:Biomarkers / Q000097:blood*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use; D019782:Riluzole / Q000627:therapeutic use
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D015415:Biomarkers; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D019782:Riluzole