Constitutive activation of pro-survival pathway ameliorates aggregation of α-synuclein in dopaminergic neurons

Julia Konovalova, Piotr Chmielarz, Safak Er, Andrii Domanskyi

Research output: Conference materialsPoster

Abstract

Parkinson’s disease (PD) is an incurable neurodegenerative disorder, primarily characterized by progressive death of dopaminergic (DA) neurons and widespread accumulation of α-synuclein (α-syn) aggregates called Lewy bodies (LB). Some data suggest that α-syn aggregation is playing important role in disease onset and progression; however, formation of LB is still poorly understood. Here, we investigate the role of activation of pro-survival signaling pathway X in accumulation of α-syn and additionally its role in promoting survival of DA neurons.
In our study we utilize primary embryonic midbrain and hippocampal cultures treated with lentiviral vector to overexpress constitutively active element of pro-survival pathway X. To investigate its ability to inhibit accumulation of α-syn, we use our previously established model of α-syn aggregation by seeding preformed fibrils (PFFs) in midbrain and hippocampal cultures with subsequent quantification of phospho-αsyn aggregates in TH- and NeuN-positive cells, respectively. Additionally, we study neuroprotective properties of active element X against ER stress by treating cells with thapsigargin for 48 hours and then quantifying number of TH-positive cells.
Here we demonstrate that activation of pro-survival signaling pathway X is capable of interfering with formation of LB-like structures in primary DA and hippocampal neurons and additionally ameliorate ER stress-induced DA neuronal loss, modulated by thapsigargin treatment. Furthermore, we investigate mechanism of its action and confirm this data in vivo.
Original languageEnglish
Publication statusPublished - 4 Jun 2019
MoE publication typeNot Eligible
Event5th World Parkinson's Congress - Kyoto Conference Center, Kyoto, Japan
Duration: 4 Jun 20197 Jun 2019

Conference

Conference5th World Parkinson's Congress
Abbreviated titleWPC 2019
CountryJapan
CityKyoto
Period04/06/201907/06/2019

Fields of Science

  • 1182 Biochemistry, cell and molecular biology

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