The Role of Autophagy and Mitochondrial Dynamics in Neurodegenerative Diseases: A Study in an Alzheimer Disease Model

Kan B., Ulus İ. H. , Öz Arslan D.

Jubilee Scientific Conference "Medicine of the Future" - 29-31 October 2020 on the occasion of the 75th Anniversary of Medical University of Plovdiv, 29 - 31 October 2020, vol.62, pp.19-20

  • Publication Type: Conference Paper / Summary Text
  • Volume: 62
  • Page Numbers: pp.19-20
  • Acibadem Mehmet Ali Aydinlar University Affiliated: Yes


The Role of Autophagy and Mitochondrial Dynamics in Neurodegenerative Diseases: A Study in an Alzheimer Disease Model

Beki Kan1, Begum Bilge1, Suleyman Bozkurt1, Ismail Hakki Ulus2 and Devrim Oz-Arslan1*

Acibadem Mehmet Ali Aydinlar University, School of Medicine, Departments of 1Biophysics and2 Medical Pharmacology, Istanbul, Turkey

*Corresponding author

Autophagy is an essential, highly conserved intracellular pathway involved in preserving cellular homeostasis by degradation of proteins, lipids, and organelles. Under normal conditions, autophagy occurs at basal levels, but it is induced by several stress conditions, including nutrient starvation, damaged organelles, aggregated proteins, DNA damage and infection.

Cytidine-5'-diphosphocholine (CDP-Ch), an intermediate in the biosynthesis of membrane phospholipids, is known to have neuroprotective effects in several diseases but the underlying precise mechanism remains elusive. The fact that choline is also involved in programmed cell death and apoptosis suggests that its protective actions may be associated with autophagy.

Recent studies suggest that autophagy may have a crucial role in Alzheimer’s disease (AD). Phosphatidylcholine (PC), one of the essential membrane components synthesized by cytidine 5’-diphosphocholine, may play a role in the formation of autophagic vesicle membranes. In this study, we aimed to understand the effect of CDP-Ch treatment on autophagy and mitochondrial dynamics during amyloid-beta (Aβ1-42) mediated neuronal injury.

To this end, nerve growth factor (NGF)-differentiated PC12 cells were treated with 1-42 in the presence and absence of CDP-Ch. We examined the levels of several autophagic markers, including LC3B, p62, Beclin-1 and also Mitofusin-2 (Mfn-2), an outer mitochondrial membrane GTPase involved in mitochondrial fusion by immunoblotting. Mitochondrial membrane potential (MMP) and mitochondrial mass were evaluated by flow cytometry and confocal imaging after probing with mitochondria-specific dyes. Oxygen consumption rate (OCR) was measured using Agilent Seahorse XFP Cell Mito Stress Kit.

We observed increases in LC3B and Mfn-2 levels of NGF-differentiated PC12 cells upon CDP-Ch treatment. Aβ1-42 treatment of NGF-differentiated cells resulted in increased levels of autophagic markers, LC3B and Beclin-1. Beta-amyloid injury changed mitochondrial membrane potential and MitoSOX levels. CDP-Ch pre-treatment of injured cells reduced MitoSox levels. The increases observed in Mfn-2 and mitochondrial mass of untreated cells suggested that CDP-Ch may be involved in mitochondrial dynamics.  

Our data indicate that CDP-Ch treatment and amyloid beta injury affect autophagy and mitochondrial function in NGF-differentiated PC12 cells and that CDP-Ch may elicit different effects depending on the degree of damage in the cell. An understanding of the role of CDP- Ch in autophagy and mitochondrial dynamics may shed light into its neuroprotective effects.

This work is supported by The Scientific and Technological Research Council of Turkey (Grant number:114Z494).