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

Julia Konovalova, Piotr Chmielarz, Safak Er, Andrii Domanskyi

Tutkimustuotos: KonferenssimateriaalitPosterivertaisarvioitu

Abstrakti

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.
Alkuperäiskielienglanti
TilaJulkaistu - 4 kesäkuuta 2019
OKM-julkaisutyyppiEi sovellu
Tapahtuma5th World Parkinson's Congress - Kyoto Conference Center, Kyoto, Japani
Kesto: 4 kesäkuuta 20197 kesäkuuta 2019

Konferenssi

Konferenssi5th World Parkinson's Congress
LyhennettäWPC 2019
MaaJapani
KaupunkiKyoto
Ajanjakso04/06/201907/06/2019

Tieteenalat

  • 1182 Biokemia, solu- ja molekyylibiologia

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