Emerging Role of PD-1 in the Central Nervous System and Brain Diseases.

Journal Article (Journal Article;Review)

Programmed cell death protein 1 (PD-1) is an immune checkpoint modulator and a major target of immunotherapy as anti-PD-1 monoclonal antibodies have demonstrated remarkable efficacy in cancer treatment. Accumulating evidence suggests an important role of PD-1 in the central nervous system (CNS). PD-1 has been implicated in CNS disorders such as brain tumors, Alzheimer's disease, ischemic stroke, spinal cord injury, multiple sclerosis, cognitive function, and pain. PD-1 signaling suppresses the CNS immune response via resident microglia and infiltrating peripheral immune cells. Notably, PD-1 is also widely expressed in neurons and suppresses neuronal activity via downstream Src homology 2 domain-containing protein tyrosine phosphatase 1 and modulation of ion channel function. An improved understanding of PD-1 signaling in the cross-talk between glial cells, neurons, and peripheral immune cells in the CNS will shed light on immunomodulation, neuromodulation, and novel strategies for treating brain diseases.

Full Text

Duke Authors

Cited Authors

  • Zhao, J; Roberts, A; Wang, Z; Savage, J; Ji, R-R

Published Date

  • August 2021

Published In

Volume / Issue

  • 37 / 8

Start / End Page

  • 1188 - 1202

PubMed ID

  • 33877518

Pubmed Central ID

  • PMC8353059

Electronic International Standard Serial Number (EISSN)

  • 1995-8218

Digital Object Identifier (DOI)

  • 10.1007/s12264-021-00683-y


  • eng

Conference Location

  • Singapore