Uncovering discrete synaptic proteomes to understand neurological disorders

Yi Zhi Wang, Jeffrey N. Savas*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations

Abstract

The mammalian nervous system is an immensely heterogeneous organ composed of a diverse collection of neuronal types that interconnect in complex patterns. Synapses are highly specialized neuronal cell-cell junctions with common and distinct functional characteristics that are governed by their protein composition or synaptic proteomes. Even a single neuron can possess a wide-range of different synapse types and each synapse contains hundreds or even thousands of proteins. Many neurological disorders and diseases are caused by synaptic dysfunction within discrete neuronal populations. Mass spectrometry (MS)-based proteomic analysis has emerged as a powerful strategy to characterize synaptic proteomes and potentially identify disease driving synaptic alterations. However, most traditional synaptic proteomic analyses have been limited by molecular averaging of proteins from multiple types of neurons and synapses. Recently, several new strategies have emerged to tackle the 'averaging problem'. In this review, we summarize recent advancements in our ability to characterize neuron-type specific and synapse-type specific proteomes and discuss strengths and limitations of these emerging analysis strategies.

Original languageEnglish (US)
Article number30
JournalProteomes
Volume6
Issue number3
DOIs
StatePublished - Sep 1 2018

Keywords

  • Axons
  • Basal ganglia
  • Dendrites
  • Neurodegeneration
  • Neuronal circuits
  • Proteomics
  • Synapse specificity
  • Synapses

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

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