Parkinson's disease involves autophagy and abnormal distribution of cathepsin L.
Accumulating evidences suggest that the related autophagy-lysosomal mechanism plays a critical role in many neurodegenerative disorders. In this study, we examined postmortem Parkinson's disease (PD) substantia nigra for evidence of cathepsin L by immunofluorescent staining, and found increased expression of cathepsin L in dopamine neurons of PD patients. We confirmed 6-OHDA induced nuclear translocation of cathepsin L in rat substantia nigral neurons as well. Furthermore, we observed autophagic vacuoles and lysosomes were accumulated in the 6-hydroxydopamine (6-OHDA) injured rat substantia nigra neurons with electron microscopy. Immunofluorescent staining showed that LC3 was enriched in dopamine neurons after 6-OHDA treatment. When pretreated with 3-methyladenine (3-MA), dopaminergic neurons were protected from cell death induced by 6-OHDA, associated with the suppression of LC3 and cathepsin L. Our results demonstrate that activation of autophagy and abnormal distribution of cathepsin L may be responsible for dopamine neuron death, involved in the pathogenic cascade event for the development of Parkinson's disease.
Department of Pharmacology, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, China.
Lingyun
L
Li
Xiaoxia
X
Wang
Xifeng
X
Fei
Liping
L
Xia
Zhenghong
Z
Qin
Zhongqin
Z
Liang
D000818:Animals; D001343:Autophagy; D056668:Cathepsin L / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology
C534281:CTSL protein, human; D056668:Cathepsin L; C534280:Ctsl protein, rat