The Nerve Growth Factor Receptor (NGFR/p75NTR): A Major Player in Alzheimer's Disease

Int J Mol Sci. 2023 Feb 6;24(4):3200. doi: 10.3390/ijms24043200.

Abstract

Alzheimer's disease (AD) represents the most prevalent type of dementia in elderly people, primarily characterized by brain accumulation of beta-amyloid (Aβ) peptides, derived from Amyloid Precursor Protein (APP), in the extracellular space (amyloid plaques) and intracellular deposits of the hyperphosphorylated form of the protein tau (p-tau; tangles or neurofibrillary aggregates). The Nerve growth factor receptor (NGFR/p75NTR) represents a low-affinity receptor for all known mammalians neurotrophins (i.e., proNGF, NGF, BDNF, NT-3 e NT-4/5) and it is involved in pathways that determine both survival and death of neurons. Interestingly, also Aβ peptides can blind to NGFR/p75NTR making it the "ideal" candidate in mediating Aβ-induced neuropathology. In addition to pathogenesis and neuropathology, several data indicated that NGFR/p75NTR could play a key role in AD also from a genetic perspective. Other studies suggested that NGFR/p75NTR could represent a good diagnostic tool, as well as a promising therapeutic target for AD. Here, we comprehensively summarize and review the current experimental evidence on this topic.

Keywords: Alzheimer’s disease; NGFR; amyloid-beta; diagnosis; expression; nerve growth factor receptor; neuropathology; p75NTR; signaling pathways; treatment.

Publication types

  • Review

MeSH terms

  • Aged
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Humans
  • Mammals / metabolism
  • Nerve Growth Factor / pharmacology
  • Nerve Tissue Proteins
  • Receptor, Nerve Growth Factor / metabolism
  • Receptors, Nerve Growth Factor / metabolism
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Nerve Growth Factor
  • Nerve Tissue Proteins
  • NGFR protein, human
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor
  • tau Proteins

Grants and funding

This work was supported by funds granted by the Italian Ministry of Health—Ricerca FinalizzataStarting Grant 2018: SG-2018-12366233.