Abstract

Lactoferrin (LF) was used at first as a vehicle to deliver non-soluble active compounds to the body, including the central nervous system (CNS). Nonetheless, it soon became evident that, apart from acting as a vehicle, LF itself owns active effects in the CNS. In the present study, the effects of LF are assessed both in baseline conditions, as well as to counteract methamphetamine (METH)-induced neurodegeneration by assessing cell viability, cell phenotype, mitochondrial status, and specific autophagy steps. In detail, cell integrity in baseline conditions and following METH administration was carried out by using H&E staining, Trypan blue, Fluoro Jade B, and WST-1. Western blot and immuno-fluorescence were used to assess the expression of the neurofilament marker βIII-tubulin. Mitochondria were stained using Mito Tracker Red and Green and were further detailed and quantified by using transmission electron microscopy. Autophagy markers were analyzed through immuno-fluorescence and electron microscopy. LF counteracts METH-induced degeneration. In detail, LF significantly attenuates the amount of cell loss and mitochondrial alterations produced by METH; and mitigates the dissipation of autophagy-related proteins from the autophagy compartment, which is massively induced by METH. These findings indicate a protective role of LF in the molecular mechanisms of neurodegeneration.

Highlights

  • Lactoferrin (LF) is an 80 kDa iron-binding multifunctional glycoprotein belonging to the transferrin family [1]

  • LF significantly attenuates the amount of cell loss and mitochondrial alterations produced by METH; and mitigates the dissipation of autophagy-related proteins from the autophagy compartment, which is massively induced by METH

  • The present study investigates the following: (i) whether LF is beneficial or detrimental for cell viability; (ii) whether LF neuroprotection following METH occurs; (iii) whether this occurs as a cell autonomous activity, independently by Nutrients 2021, 13, 3356 concomitant mechanisms; (iv) and whether this relies on specific subcellular targets such as the autophagy machinery and mitochondria

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Summary

Introduction

Lactoferrin (LF) is an 80 kDa iron-binding multifunctional glycoprotein belonging to the transferrin family [1]. It is highly conserved among mammalian species [2,3,4,5,6]. LF was used at first as a vehicle to deliver non-soluble active compounds to the body, including the central nervous system (CNS) [11,12,13,14,15,16,17,18]. It soon became evident that, apart from acting as a vehicle, LF itself owns active effects in the CNS. Strong protective effects are hypothesized to take place in a variety of neuropathological conditions, including degenerative disorders [19]

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