Tags

Type your tag names separated by a space and hit enter

Curcumin ameliorates the neurodegenerative pathology in A53T α-synuclein cell model of Parkinson's disease through the downregulation of mTOR/p70S6K signaling and the recovery of macroautophagy.
J Neuroimmune Pharmacol. 2013 Mar; 8(1):356-69.JN

Abstract

Parkinson's disease (PD) is pathologically characterized by the presence of α-synuclein positive intracytoplasmic inclusions. The missense mutation, A53T α-synuclein is closely related to hereditary, early-onset PD. Accumulating evidences suggest that pathological accumulation of A53T α-synuclein protein will perturb itself to be efficiently and normally degraded through its usual degradation pathway, macroautophagy-lysosome pathway, therefore toxic effects on the neuron will be exacerbated. Based on the above fact, we demonstrated in this study that A53T α-synuclein overexpression impairs macroautophagy in SH-SY5Y cells and upregulates mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) signaling, the classical suppressive pathway of autophagy. We further found that curcumin, a natural compound derived from the curry spice turmeric and with low toxicity in normal cells, could efficiently reduce the accumulation of A53T α-synuclein through downregulation of the mTOR/p70S6K signaling and recovery of macroautophagy which was suppressed. These findings suggested that the regulation of mTOR/p70S6K signaling may be a participant of the accumulation of A53T α-synuclein protein-linked Parkinsonism. Meanwhile curcumin could be a candidate neuroprotective agent by inducing macroautophagy, and needs to be further investigated by clinical application in patients suffering Parkinson's disease.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Jiang TF
Department of Neurology & Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Zhang YJ
No affiliation info available
Zhou HY
No affiliation info available
Wang HM
No affiliation info available
Tian LP
No affiliation info available
Liu J
No affiliation info available
Ding JQ
No affiliation info available
Chen SD
No affiliation info available

MeSH

AdenineAutophagyBlotting, WesternCell LineCell SurvivalCurcuminGenetic VectorsHumansImmunohistochemistryMacrophagesNeurodegenerative DiseasesNeuroprotective AgentsParkinson DiseaseRibosomal Protein S6 Kinases, 70-kDaTOR Serine-Threonine KinasesTransfectionalpha-Synuclein

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23325107

Citation

Jiang, Tian-Fang, et al. "Curcumin Ameliorates the Neurodegenerative Pathology in A53T Α-synuclein Cell Model of Parkinson's Disease Through the Downregulation of mTOR/p70S6K Signaling and the Recovery of Macroautophagy." Journal of Neuroimmune Pharmacology : the Official Journal of the Society On NeuroImmune Pharmacology, vol. 8, no. 1, 2013, pp. 356-69.
Jiang TF, Zhang YJ, Zhou HY, et al. Curcumin ameliorates the neurodegenerative pathology in A53T α-synuclein cell model of Parkinson's disease through the downregulation of mTOR/p70S6K signaling and the recovery of macroautophagy. J Neuroimmune Pharmacol. 2013;8(1):356-69.
Jiang, T. F., Zhang, Y. J., Zhou, H. Y., Wang, H. M., Tian, L. P., Liu, J., Ding, J. Q., & Chen, S. D. (2013). Curcumin ameliorates the neurodegenerative pathology in A53T α-synuclein cell model of Parkinson's disease through the downregulation of mTOR/p70S6K signaling and the recovery of macroautophagy. Journal of Neuroimmune Pharmacology : the Official Journal of the Society On NeuroImmune Pharmacology, 8(1), 356-69. https://doi.org/10.1007/s11481-012-9431-7
Jiang TF, et al. Curcumin Ameliorates the Neurodegenerative Pathology in A53T Α-synuclein Cell Model of Parkinson's Disease Through the Downregulation of mTOR/p70S6K Signaling and the Recovery of Macroautophagy. J Neuroimmune Pharmacol. 2013;8(1):356-69. PubMed PMID: 23325107.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Curcumin ameliorates the neurodegenerative pathology in A53T α-synuclein cell model of Parkinson's disease through the downregulation of mTOR/p70S6K signaling and the recovery of macroautophagy. AU - Jiang,Tian-Fang, AU - Zhang,Ying-Jie, AU - Zhou,Hai-Yan, AU - Wang,Hong-Mei, AU - Tian,Li-Peng, AU - Liu,Jun, AU - Ding,Jian-Qing, AU - Chen,Sheng-Di, Y1 - 2013/01/17/ PY - 2012/09/01/received PY - 2012/12/19/accepted PY - 2013/1/18/entrez PY - 2013/1/18/pubmed PY - 2013/8/21/medline SP - 356 EP - 69 JF - Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology JO - J Neuroimmune Pharmacol VL - 8 IS - 1 N2 - Parkinson's disease (PD) is pathologically characterized by the presence of α-synuclein positive intracytoplasmic inclusions. The missense mutation, A53T α-synuclein is closely related to hereditary, early-onset PD. Accumulating evidences suggest that pathological accumulation of A53T α-synuclein protein will perturb itself to be efficiently and normally degraded through its usual degradation pathway, macroautophagy-lysosome pathway, therefore toxic effects on the neuron will be exacerbated. Based on the above fact, we demonstrated in this study that A53T α-synuclein overexpression impairs macroautophagy in SH-SY5Y cells and upregulates mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) signaling, the classical suppressive pathway of autophagy. We further found that curcumin, a natural compound derived from the curry spice turmeric and with low toxicity in normal cells, could efficiently reduce the accumulation of A53T α-synuclein through downregulation of the mTOR/p70S6K signaling and recovery of macroautophagy which was suppressed. These findings suggested that the regulation of mTOR/p70S6K signaling may be a participant of the accumulation of A53T α-synuclein protein-linked Parkinsonism. Meanwhile curcumin could be a candidate neuroprotective agent by inducing macroautophagy, and needs to be further investigated by clinical application in patients suffering Parkinson's disease. SN - 1557-1904 UR - https://www.unboundmedicine.com/medline/citation/23325107/Curcumin_ameliorates_the_neurodegenerative_pathology_in_A53T_α_synuclein_cell_model_of_Parkinson's_disease_through_the_downregulation_of_mTOR/p70S6K_signaling_and_the_recovery_of_macroautophagy_ L2 - https://doi.org/10.1007/s11481-012-9431-7 DB - PRIME DP - Unbound Medicine ER -