14-3-3 protein and its isoforms: A common diagnostic marker for Alzheimer's disease, Parkinson's disease and glaucomatous neurodegeneration

Ageing Res Rev. 2024 Dec:102:102572. doi: 10.1016/j.arr.2024.102572. Epub 2024 Nov 1.

Abstract

There is a molecular coupling between neurodegenerative diseases, including glaucomatous neurodegeneration (GN), Alzheimer's disease (AD), and Parkinson's disease (PD). Many cells in the eye and the brain have the right amount of 14-3-3 proteins (14-3-3 s) and their isoforms, such as β, ε, γ, η, θ, π, and γ. These cells include keratocytes, endothelial cells, corneal epithelial cells, and primary conjunctival epithelial cells. 14-3-3 s regulate autophagy and mitophagy, help break down built-up proteins, and connect to other proteins to safeguard against neurodegeneration in AD, PD, GN, and glioblastoma. By interacting with these proteins, 14-3-3 s stop Bad and Bax proteins from entering mitochondria and make them less effective. These interactions inhibit neuronal apoptosis. They play many important roles in managing the breakdown of lysosomal proteins, tau, and Aβ, which is why the 14-3-3 s could be used as therapeutic targets in AD. Furthermore, researchers have discovered 14-3-3 s in Lewy bodies, which are associated with various proteins like LRRK2, ASN, and Parkin, all of which play a role in developing Parkinson's disease (PD). The 14-3-3 s influence the premature aging and natural wrinkles of human skin. Studies have shown that lowering 14-3-3 s in the brain can lead to an increase in cell-death proteins like BAX and ERK, which in turn causes excitotoxicity-induced neurodegeneration. This review aimed to clarify the role of 14-3-3 s in the neuropathology of AD, PD, and GN, as well as potential diagnostic markers for improving neuronal survival and repair.

Keywords: 14–3–3 s; Alzheimer’s disease; Glaucomatous neurodegeneration; Parkinson’s disease.

Publication types

  • Review

MeSH terms

  • 14-3-3 Proteins* / metabolism
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Animals
  • Biomarkers* / metabolism
  • Glaucoma* / diagnosis
  • Glaucoma* / metabolism
  • Glaucoma* / pathology
  • Humans
  • Parkinson Disease* / diagnosis
  • Parkinson Disease* / metabolism
  • Parkinson Disease* / pathology
  • Protein Isoforms* / metabolism

Substances

  • 14-3-3 Proteins
  • Protein Isoforms
  • Biomarkers