Parkin, PINK1 and DJ1 as possible modulators of mTOR pathway in ganglioglioma

ABSTRACT

Purpose: Ganglioglioma (GG) is a non-malignant tumor classified as G1 by the WHO. Although we currently know that the neoplasm may result from the hyperactivity of protein kinase B (PKB or Akt) or extracellular-regulated kinase (Erk), which upregulates mammalian target of rapamycin kinase (mTOR) and leads to translation of proteins responsible for cell cycle regulation, there are still many questions to be answered. In the current paper we try to analyze the link between GG formation and activity of three proteins known to play a role in neuroprotection (parkin, PINK1 and DJ1).

Materials and Methods: In our paper, we review the current information on the involvement of these proteins in the transmission of information in the cell and triggering various cell signals, like survival or apoptosis. We also review current literature data on involvement of parkin, DJ1 and PINK1 in the regulation of mTOR, the pathway probably contributing to the development of GG.

Results: Parkin is an E3 ubiquitin ligase, shown to trigger proteasome-dependent degradation and autophagy, necessary for the maintenance of homeostasis in neurons. PINK1, a mitochondrial protein kinase, is required for mitochondrial maintenance and neuronal survival. DJ1 is a sensor of reactive oxygen species, and protects the cells against oxidative stress. Mutations in the genes encoding these three proteins are known to underlie autosomal recessive forms of Parkinson's disease, as well as other neurodegenerative and neuroinflammatory disorders.

Conclusion: It appears that mutations of parkin, PINK1 and DJ1 may result in the development of both neurodegeneration and tumors. Also, these proteins might be used as markers of disease, thus allowing better diagnosis and therapy.

KEYWORDS:

• mTOR
• parkin
• PINK1
• DJ1
• ganglioglioma

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper.

Additional information

Notes on contributors

Katarzyna Drapalo

Katarzyna Drapalo, MSc, graduated from the Institute of Applied Biotechnology and Basic Sciences of the University of Rzeszow, Poland. Her master's thesis concerned the role of inflammation in the pathophysiology of depression. In 2014, she was elected for the position of a biologist at the Department of Histology and Embryology, Warsaw Medical University, Poland.

Jaroslaw Jozwiak

Jarosław Jozwiak, MD, MSc, PhD, graduated from the Chemical Faculty of the Warsaw University of Technology, Warsaw, Poland and Warsaw Medical University (WMU), Warsaw, Poland. He won the competition for the best biochemical student in Poland organized by Procter&Gamble. In 2002, he defended doctor's thesis at the WMU. In 2003, he was elected for the position of an assistant professor at the WMU. He was awarded several scientific awards of the WMU, Polish Academy of Sciences, Minister of Health and Prime Minister of Poland. Currently, he studies the regulation of the mTOR pathway and its implications in tuberous sclerosis.