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

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.