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

T Colasanti (1, 2) , M Vomero (1) , C Alessandri (3) , C Barbati (1, 4) , A Maselli (1) , C Camperio (5) , F Conti (3) , A Tinari (6) , C Carlo-Stella (7, 8) , L Tuosto (5) , D Benincasa (9, 10) , G Valesini (3) , W Malorni (4, 11) , M Pierdominici (1) , E Ortona (1, 4)

1 Department of Cell Biology and Neurosciences
2 Department of Medical Sciences
3 Department of Internal Medicine, Lupus Clinic
4 Department of Medical Sciences
5 Department of Biology and Biotechnology "Charles Darwin"
6 Department of Technology and Health
7 Department of Oncology and Hematology, Humanitas Cancer Center
8 Department of Medical Biotechnology and Translational Medicine
9 Laboratory of Clinical and Behavioral Neurology
10 Movement Disorder Unit, Sant’Andrea Hospital
11 Department of Therapeutic Research and Medicine Evaluation

It has been demonstrated that α-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 α-synuclein in the autophagy process in primary human T lymphocytes. We provide evidence that: (i) knocking down of the α-synuclein gene resulted in increased autophagy, (ii) autophagy induction by energy deprivation was associated with a significant decrease of α-synuclein levels, (iii) autophagy inhibition by 3-methyladenine or by ATG5 knocking down led to a significant increase of α-synuclein levels, and (iv) autophagy impairment, constitutive in T lymphocytes from patients with systemic lupus erythematosus, was associated with abnormal accumulation of α-synuclein aggregates. These results suggest that α-synuclein could be considered as an autophagy-related marker of peripheral blood lymphocytes, potentially suitable for use in the clinical practice.

Domains: Biochemistry, Molecular Biology; Immunology

T Colasanti, M Vomero, C Alessandri, C Barbati, A Maselli, et al.. Role of alpha-synuclein in autophagy modulation of primary human T lymphocytes.. Cell Death and Disease, 2014, 5, pp.e1265. ⟨10.1038/cddis.2014.211⟩. ⟨pasteur-01197320⟩