Diseases of the Synaptic Vesicle: A Potential New Group of Neurometabolic Disorders Affecting Neurotransmission

Semin Pediatr Neurol. 2016 Nov;23(4):306-320. doi: 10.1016/j.spen.2016.11.005. Epub 2016 Nov 15.

Abstract

The general concept of inborn error of metabolism is currently evolving into the interface between classical biochemistry and cellular biology. Basic neuroscience is providing increasing knowledge about the mechanisms of neurotransmission and novel related disorders are being described. There is a necessity of updating the classic concept of "inborn error of neurotransmitters (NT)" that considers mainly defects of synthesis and catabolism and transport of low weight NT molecules. Monogenic defects of the synaptic vesicle (SV), and especially those affecting the SV cycle are a potential new group of NT disorders since they end up in abnormal NT turnover and release. The most common clinical manifestations include epilepsy, intellectual disability, autism and movement disorders, and are in the continuum symptoms of synaptopathies. Interestingly, brain malformations and neurodegenerative conditions are also present within SV diseases. Metabolomics, proteomics, and other -omic techniques probably will provide biomarkers and contribute to therapeutic targets in the future.

Publication types

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

MeSH terms

  • Brain Diseases, Metabolic, Inborn / complications*
  • Congenital Abnormalities / etiology*
  • Epilepsy / etiology*
  • Humans
  • Intellectual Disability / etiology*
  • Movement Disorders / etiology*
  • Neurodegenerative Diseases / etiology*
  • Neuromuscular Diseases / etiology*
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / pathology*