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

Julia Konovalova, Piotr Chmielarz, Safak Er, Andrii Domanskyi

Forskningsoutput: KonferensbidragPoster

Sammanfattning

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.
Originalspråkengelska
StatusPublicerad - 4 jun 2019
MoE-publikationstypEj behörig
Evenemang5th World Parkinson's Congress - Kyoto Conference Center, Kyoto, Japan
Varaktighet: 4 jun 20197 jun 2019

Konferens

Konferens5th World Parkinson's Congress
Förkortad titelWPC 2019
LandJapan
OrtKyoto
Period04/06/201907/06/2019

Vetenskapsgrenar

  • 1182 Biokemi, cell- och molekylärbiologi

Citera det här

Konovalova, J., Chmielarz, P., Er, S., & Domanskyi, A. (2019). Constitutive activation of pro-survival pathway ameliorates aggregation of α-synuclein in dopaminergic neurons. Poster presenterad vid 5th World Parkinson's Congress, Kyoto, Japan.