Neurotrophin-targeted therapeutics: A gateway to cognition and more?

Drug Discov Today. 2022 Oct;27(10):103318. doi: 10.1016/j.drudis.2022.07.003. Epub 2022 Jul 16.

Abstract

Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), are small proteins expressed in the brain and peripheral tissues, which regulate several key aspects of neuronal function, including neurogenesis, synaptic plasticity and neuroprotection, but also programmed cell death. This broad range of effects is a result of a complex downstream signaling pathway, with differential spatial and temporal activation patterns further diversifying their physiological effects. Alterations in neurotrophin levels, or known polymorphisms in neurotrophin genes, have been linked to a variety of disorders, including depression and Alzheimer's disease (AD). Historically, their therapeutic potential in these disorders has been hampered by the lack of suitable tool molecules for clinical studies. However, recent advancements have led to the development of new therapeutic candidates, which are now in clinical testing.

Keywords: Alzheimer’s disease; Depression; Neurotrophins; TrkA; TrkB.

Publication types

  • Review

MeSH terms

  • Brain-Derived Neurotrophic Factor* / genetics
  • Brain-Derived Neurotrophic Factor* / metabolism
  • Cognition
  • Nerve Growth Factor*
  • Receptors, Nerve Growth Factor / genetics
  • Signal Transduction / physiology

Substances

  • Brain-Derived Neurotrophic Factor
  • Receptors, Nerve Growth Factor
  • Nerve Growth Factor