title: Stimulation of autophagy prevents amyloid-β peptide-induced neuritic degeneration in PC12 cells.
abstract: Autophagy is a lysosomal degradative process essential for neuronal homeostasis, whereas autophagic failure has been linked to accumulating neurodegenerative disorders. However, the precise role of autophagy in axonal and dendritic degeneration in Alzheimer's disease (AD) remains unclear. In this study, we aim to investigate the precise effect of autophagy in amyloid-β peptide (Aβ)25-35-mediated neurite degeneration. Aβ35-25, the non-neurotoxic reverse sequence analogue of Aβ25-35, was used as a negative control. Our results showed that Aβ25-35 dose-dependently suppressed PC12 proliferation and induced autophagy induction in neurites (axons and dendrites). A high proportion of autophagic structures in PC12 neurites were autolysosomes after 24 h of Aβ25-35 treatment. Autophagy inhibition by 3-methyladenine (3MA), LY294002, and chloroquine (CQ) could not relieve the Aβ25-35-induced neurite degeneration, while administration of autophagy stimulator rapamycin or AR-12 efficiently suppressed neurite degeneration. Autophagosomes colocalized with fragmented mitochondria after Aβ25-35 treatment. Similar results were obtained using in vitro cultured superior cervical ganglion neurons. These findings demonstrate that autophagy stimulation may prevent neuritic degeneration following Aβ25-35 treatment. Upregulation of autophagic activity may provide a valuable approach for the treatment of axonal and dendritic dystrophy in AD patients.
authors: Department of Pharmacology, Hangzhou Key Laboratory of Medical Neurobiology, School of Medicine, Hangzhou Normal University, Hangzhou, P.R. China Qiushi Academy of Advanced Studies, Zhejiang University, Hangzhou, P.R. China Department of Biomedical Engineering, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, P.R. China.
authors: Yi
authors: Y
authors: Yang
authors: Department of Biomedical Engineering, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, P.R. China.
authors: Sicong
authors: S
authors: Chen
authors: Department of Pharmacology, Hangzhou Key Laboratory of Medical Neurobiology, School of Medicine, Hangzhou Normal University, Hangzhou, P.R. China.
authors: Jiafeng
authors: J
authors: Zhang
authors: Department of Pharmacology, Hangzhou Key Laboratory of Medical Neurobiology, School of Medicine, Hangzhou Normal University, Hangzhou, P.R. China.
authors: Chentan
authors: C
authors: Li
authors: Department of Biomedical Engineering, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, P.R. China.
authors: Yonghong
authors: Y
authors: Sun
authors: Department of Pharmacology, Hangzhou Key Laboratory of Medical Neurobiology, School of Medicine, Hangzhou Normal University, Hangzhou, P.R. China.
authors: Lihui
authors: L
authors: Zhang
authors: Qiushi Academy of Advanced Studies, Zhejiang University, Hangzhou, P.R. China Department of Biomedical Engineering, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, P.R. China.
authors: Xiaoxiang
authors: X
authors: Zheng
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology* / Q000517:prevention & control; D016501:Neurites / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D009474:Neurons / Q000473:pathology; D009924:Organ Culture Techniques; D016716:PC12 Cells / Q000166:cytology; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017783:Superior Cervical Ganglion / Q000166:cytology
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35)
keywords: Alzheimer's disease; amyloid-β peptide; autophagy; neuritic degeneration