Deciphering cell-type specific signal transduction in the brain: Challenges and promises

Adv Pharmacol. 2021;90:145-171. doi: 10.1016/bs.apha.2020.09.009. Epub 2020 Oct 19.

Abstract

Signal transduction designates the set of molecular events that take place within a cell upon extracellular stimulation to mediate a functional outcome. Decades after the discovery that dopamine triggers opposing signaling pathways in D1- and D2-expressing medium spiny neurons, it is now clear that there are as many different flavors of signaling pathways in the brain as there are neuron types. One of the biggest challenges in molecular neuroscience is to elucidate cell-type specific signaling, in order to understand neurological diseases with regional vulnerability, but also to identify targets for precision drugs devoid of off-target effects. Here, we make a case for the importance of the study of neuron-type specific molecular characteristics. We then review the technologies that exist to study neurons in their full diversity and highlight their disease-relevant idiosyncrasies.

Keywords: Cell-type specific; Neurodegenerative disease; Nucleus sorting; Paul Greengard; Psychiatric disease; Selective neuronal vulnerability; Signal transduction; Single-nucleus RNAseq; Systems-level; bacTRAP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / metabolism*
  • Drug Development
  • Drug Repositioning
  • Humans
  • Nervous System Diseases / metabolism
  • Signal Transduction*
  • Systems Biology