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Front. Mol. Neurosci. | doi: 10.3389/fnmol.2018.00465

Could α-Synuclein Modulation of Insulin and Dopamine Identify a Novel Link between Parkinson’s Disease and Diabetes as well as Potential Therapies?

 Ruth G. Perez1*, Barbara Yang1 and Javier Vargas-Medrano1
  • 1Texas Tech University Health Sciences Center El Paso, United States

Characterizing the normal function(s) of the protein α-Synuclein (aSyn) has the potential to illuminate links between Parkinson’s disease (PD) and diabetes and also point the way toward new therapies for these disorders. Here we provide a perspective for consideration based on our discovery that aSyn normally acts to inhibit insulin secretion from pancreatic β-cells by interacting with the Kir6.2 subunit of the ATP-sensitive potassium channel (K-ATP). It is also known that K-ATP channels act to inhibit brain dopamine secretion, and we have also shown that aSyn is a normal inhibitor of dopamine synthesis. The finding that aSyn modulates Kir6.2 and other proteins involved in dopamine and insulin secretion, suggest that aSyn interacting proteins may be negatively impacted when aSyn aggregates inside cells. Furthermore, identifying therapies for PD that can counteract dysfunctions found in diabetes, would be highly beneficial. One such compound may be the multiple sclerosis drug, FTY720, which like aSyn can stimulate the activity of the catalytic subunit of protein phosphatase 2A (PP2Ac) as well as insulin secretion. In aging aSyn transgenic mice given long term oral FTY720, the mice had reduced aSyn pathology and increased levels of the protective molecule, brain derived neurotrophic factor (BDNF) [1]. In collaboration with medicinal chemists, we made two non-immunosuppressive FTY720s that also enhance PP2Ac activity and BDNF expression [2; 3; 4]. FTY720 and our novel FTY720-based-derivatives, may thus have therapeutic potential for both diabetes and PD.

Keywords: alpha-Synuclein, Kir6.2 channel, Dopamine, Insulin, Parkinson ’s disease, Type 2 diabete mellitus, lag3

Received: 19 Oct 2018; Accepted: 30 Nov 2018.

Edited by:

Yunjong Lee, Sungkyunkwan University, South Korea

Reviewed by:

Ali Keshavarzian, Rush University, United States
Xiaobo Mao, School of Medicine, Johns Hopkins University, United States  

Copyright: © 2018 Perez, Yang and Vargas-Medrano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Ruth G. Perez, Texas Tech University Health Sciences Center El Paso, El Paso, United States, ruth.g.perez@ttuhsc.edu