Premium
Alteration of the autophagy‐lysosomal system in models of Parkinson's disease
Author(s) -
Pivtoraiko Violetta Nikolaevna,
Schacka John,
Roth Kevin
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.356.3
Subject(s) - autophagy , programmed cell death , lysosome , cathepsin d , apoptosis , microbiology and biotechnology , sh sy5y , neurodegeneration , rotenone , caspase , vacuole , biology , chemistry , mitochondrion , biochemistry , enzyme , cell culture , neuroblastoma , medicine , disease , cytoplasm , genetics
In Parkinson's disease (PD), increasing evidence suggests that neuron death may be related to alterations in the autophagy‐lysosomal pathway (ALP). To further investigate the role of the ALP in neuron death regulation in PD models, differentiated SH‐SY5Y human neuroblastoma cells were treated with either chloroquine (CQ), known to induce autophagic neuronal death, morphologically defined by the aberrant accumulation of autophagic vacuoles (AVs) concomitant with markers of apoptosis and/or necrosis, or rotenone (Rt), a selective inhibitor of complex I of the mitochondrial electron transport chain. CQ induced AV accumulation and inhibited cathepsin D processing (lysosomal aspartic protease), suggesting a CQ‐induced compromise of the ALP. CQ promoted α‐synuclein aggregation, one of the principal hallmarks of PD, emphasizing the potential for altered lysosome function in PD. CQ‐induced an increase in caspase‐3‐like enzymatic activity. Rt‐induced cell death was also accompanied by AV accumulation and increased caspase‐3‐like enzymatic activity. However, pharmacological inhibition of caspase activity did not significantly attenuate CQ or Rt‐induced cell death. These observations suggest that alteration of the ALP may facilitate accumulation of aggregated protein and contribute to the induction of multiple types of neuron cell death in PD. This work was supported by NS57098, NS 47466, and NS35107