Identification and Characterization of Neuroprotective Properties of Thaumatin-like Protein 1a from Annurca Apple Flesh Polyphenol Extract

Nutrients. 2024 Jan 19;16(2):307. doi: 10.3390/nu16020307.

Abstract

Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are multifactorial neurodegenerative disorders that are mostly treated with drugs inhibiting key enzymes of cholinergic and aminergic neurotransmission, such as acetyl and butyryl cholinesterase (AChE, BuChE) or monoamine oxidases (MAO)-A/B, and of Aβ1-40 aggregation. Diet plant components with multitarget functions are promising compounds in the prevention of AD and PD. Our aim was to identify neuroprotective compounds from Annurca apple polyphenol extract (AFPE).

Methods: AFPE was fractionated by gel filtration, and the eluted peaks were subjected to chemical analyses (i.e., RP-HPLC and mass spectrometry), determination of inhibitory enzyme activity and cell effects by MTT, and morphology assays.

Results: In AFPE, we identified thaumatin-like protein 1a, belonging to the pathogenesis-related protein (PR) family. This protein showed the best inhibitory activity on AChE, MAO-A (IC50 = 5.53 µM and 1.71 µM, respectively), and Aβ1-40 fibril aggregation (IC50 = 9.16 µM), compared to AFPE and other polyphenol-containing fractions. Among the latter, Peak 4 reverted Aβ fibril formation (IC50 = 104.87 µM). Moreover, thaumatin-like protein 1a protected AGS and MKN-28 cells from serum-deprivation-induced stress conditions.

Conclusions: We showed that AFPE exerted neuroprotective functions not only through its polyphenols but also through thaumatin-like protein 1a, which acted like a multitarget molecule.

Keywords: Alzheimer’s disease (AD); Annurca apple polyphenols; Aβ 1–40 aggregation; Parkinson’s disease (PD); cholinesterase inhibitor; monoamine oxidase (MAO) inhibitor; thaumatin-like protein 1a.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Alzheimer Disease* / drug therapy
  • Amyloid beta-Peptides / metabolism
  • Chlorogenic Acid*
  • Cholinesterase Inhibitors / pharmacology
  • Flavonoids*
  • Food Additives / therapeutic use
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / pharmacology
  • Monoamine Oxidase Inhibitors / therapeutic use
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Parkinson Disease* / drug therapy
  • Tannins

Substances

  • apple polyphenol extract
  • Monoamine Oxidase Inhibitors
  • Monoamine Oxidase
  • Tannins
  • Amyloid beta-Peptides
  • Food Additives
  • Neuroprotective Agents
  • Cholinesterase Inhibitors
  • Acetylcholinesterase
  • Chlorogenic Acid
  • Flavonoids

Grants and funding

This research work was supported by grants from the MUR fund for the promotion and policy development of the National Research Programme (PNR)—DM 737 of 25-06-2021 CUP I55F21003620001 (R.A.), DM 1275 of 10-12-2021 CUP I69J22001050001 (M.M.), and by Next Generation EU in the framework of PRIN 2022, CUP I53D23004270006 (M.M.).