Alpha-Synuclein Glycation and the Action of Anti-Diabetic Agents in Parkinson's Disease

J Parkinsons Dis. 2018;8(1):33-43. doi: 10.3233/JPD-171285.


Parkinson's disease (PD) is a neurodegenerative disorder with complex etiology and variable pathology. While a subset of cases is associated with single-gene mutations, the majority originates from a combination of factors we do not fully understand. Thus, understanding the underlying causes of PD is indispensable for the development of novel therapeutics. Glycation, the non-enzymatic reaction between reactive dicarbonyls and amino groups, gives rise to a variety of different reaction products known as advanced glycation end products (AGEs). AGEs accumulate over a proteins life-time, and increased levels of glycation reaction products play a role in diabetic complications. It is now also becoming evident that PD patients also display perturbed sugar metabolism and protein glycation, including that of alpha-synuclein, a key player in PD. Here, we hypothesize that anti-diabetic drugs targeting the levels of glycation precursors, or promoting the clearance of glycated proteins may also prove beneficial for PD patients.

Keywords: Glycation; Maillard-reaction; Parkinson’s disease; alpha-synuclein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetes Complications / drug therapy
  • Diabetes Complications / metabolism
  • Diabetes Complications / prevention & control
  • Glucose / metabolism
  • Glycation End Products, Advanced / metabolism*
  • Glycosylation / drug effects
  • Homeostasis
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Maillard Reaction / drug effects
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism*
  • Protein Processing, Post-Translational / drug effects
  • Pyruvaldehyde / metabolism
  • Risk Factors
  • alpha-Synuclein / metabolism*


  • Glycation End Products, Advanced
  • Hypoglycemic Agents
  • alpha-Synuclein
  • Pyruvaldehyde
  • Glucose