Phosphatidic acid signaling participates in the neurodegeneration induced by α-synuclein

CONDE, M.; IGLESIAS GONZALEZ, P; ALZA, N; URANGA, R; SALVADOR GABRIELA

Cordoba

Congreso; 52 Reunion Anual de SAIB; 2016

SAIB

PHOSPHATIDIC ACID SIGNALING PARTICIPATES IN THE NEURODEGENERATIONINDUCED BY α-SYNUCLEINConde MA; Iglesias Gonzalez PA; Alza NP; Uranga RM; Salvador GAInstituto de Investigaciones Bioquímicas de Bahía Blanca-Universidad Nacional del SurE-mail: mconde@inibibb-conicet.gob.arPathological accumulation of α-synuclein (α-syn) is a hallmark of Parkinson?s disease. Even though the physiological function of thisprotein is still unknown, it is well accepted that its aggregation prompts degeneration and death in dopaminergic neurons. Oneintriguing characteristic of α-syn is its lipid binding affinity. We have previously reported that overexpression of α-syn triggers an BIOCELL 40 (Suppl.1) 2016110increase in neutral lipid and fatty acid content (SAIB 2014-2015) in dopaminergic neurons. In this work, we investigated the state ofphosphatidic acid (PA) signaling in human neurons overexpressing α-syn. Specifically, we studied the state of phospholipase D (PLD)pathway that catalyzes PA generation by phosphatidylcholine hydrolysis. We detected diminished PLD1 expression and ERKphosphorylation in α-syn neurons. Overexpression of α-syn inhibited ERK nuclear localization and the expression of the neuronalmarker neurofilament (NF). PLD1 pharmacological inhibition (EVJ) demonstrated that both ERK nuclear localization and NFexpression were dependent on this pathway. Enhancers of α-syn toxicity such as copper overload and 6-hydroxydopamine alsodisplayed differential regulation of PLD1 expression. Our results demonstrate that α-syn accumulation promotes neurodegenerationthrough the inhibition of PLD1 pathway, thus affecting ERK signaling and NF expression. Sponsored by FONCyT-CONICET-UNS