Role of alpha-synuclein in autophagy modulation of primary human T lymphocytes

被引:36
作者
Colasanti, T. [1 ,2 ]
Vomero, M. [1 ]
Alessandri, C. [3 ]
Barbati, C. [1 ,4 ]
Maselli, A. [1 ]
Camperio, C. [5 ]
Conti, F. [3 ]
Tinari, A. [6 ]
Carlo-Stella, C. [7 ,8 ]
Tuosto, L. [5 ]
Benincasa, D. [9 ,10 ]
Valesini, G. [3 ]
Malorni, W. [4 ,11 ]
Pierdominici, M. [1 ]
Ortona, E. [1 ,4 ]
机构
[1] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy
[2] San Raffaele Inst Pisana, Dept Med Sci, Rome, Italy
[3] Univ Roma La Sapienza, Dept Internal Med, Lupus Clin, Rome, Italy
[4] San Raffaele Inst Sulmona, Dept Med Sci, Laquila, Italy
[5] Univ Roma La Sapienza, Ist Pasteur, Fdn Cenci Bolognetti, Dept Biol & Biotechnol C Darwin, Rome, Italy
[6] Ist Super Sanita, Dept Technol & Hlth, I-00161 Rome, Italy
[7] Humanitas Clin & Res Ctr, Humanitas Canc Ctr, Dept Hematol & Oncol, Rozzano, MI, Italy
[8] Univ Milan, Dept Med Biotechnol & Translat Med, I-20122 Milan, Italy
[9] IRCCS, Fdn Santa Lucia, Lab Clin & Behav Neurol, Rome, Italy
[10] Univ Roma La Sapienza, SantAndrea Hosp, Movement Disorder Unit, Rome, Italy
[11] Ist Super Sanita, Dept Therapeut Res & Med Evaluat, I-00161 Rome, Italy
关键词
alpha-synuclein; T lymphocytes; autophagy; systemic lupus erythematosus; lymphoma; DISEASE-ACTIVITY; APOPTOSIS; IMMUNITY; CELL; MACROAUTOPHAGY; AGGREGATION; EXPRESSION; SORAFENIB; PATHWAYS; SURVIVAL;
D O I
10.1038/cddis.2014.211
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
It has been demonstrated that alpha-synuclein can aggregate and contribute to the pathogenesis of some neurodegenerative diseases and it is capable of hindering autophagy in neuronal cells. Here, we investigated the implication of alpha-synuclein in the autophagy process in primary human T lymphocytes. We provide evidence that: (i) knocking down of the alpha-synuclein gene resulted in increased autophagy, (ii) autophagy induction by energy deprivation was associated with a significant decrease of a-synuclein levels, (iii) autophagy inhibition by 3-methyladenine or by ATG5 knocking down led to a significant increase of alpha-synuclein levels, and (iv) autophagy impairment, constitutive in T lymphocytes from patients with systemic lupus erythematosus, was associated with abnormal accumulation of Phi-synuclein aggregates. These results suggest that alpha-synuclein could be considered as an autophagy-related marker of peripheral blood lymphocytes, potentially suitable for use in the clinical practice.
引用
收藏
页码:e1265 / e1265
页数:9
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