Spermidine Rescues Bioenergetic and Mitophagy Deficits Induced by Disease-Associated Tau Protein

Author:

Fairley Lauren H.12,Lejri Imane12,Grimm Amandine123ORCID,Eckert Anne12

Affiliation:

1. Research Cluster Molecular and Cognitive Neuroscience, University of Basel, 4002 Basel, Switzerland

2. Neurobiology Lab for Brain Aging and Mental Health, Psychiatric University Clinics, 4002 Basel, Switzerland

3. Department of Biomedicine, University of Basel, 4055 Basel, Switzerland

Abstract

Abnormal tau build-up is a hallmark of Alzheimer’s disease (AD) and more than 20 other serious neurodegenerative diseases. Mitochondria are paramount organelles playing a predominant role in cellular bioenergetics, namely by providing the main source of cellular energy via adenosine triphosphate generation. Abnormal tau impairs almost every aspect of mitochondrial function, from mitochondrial respiration to mitophagy. The aim of our study was to investigate the effects of spermidine, a polyamine which exerts neuroprotective effects, on mitochondrial function in a cellular model of tauopathy. Recent evidence identified autophagy as the main mechanism of action of spermidine on life-span prolongation and neuroprotection, but the effects of spermidine on abnormal tau-induced mitochondrial dysfunction have not yet been investigated. We used SH-SY5Y cells stably expressing a mutant form of human tau protein (P301L tau mutation) or cells expressing the empty vector (control cells). We showed that spermidine improved mitochondrial respiration, mitochondrial membrane potential as well as adenosine triphosphate (ATP) production in both control and P301L tau-expressing cells. We also showed that spermidine decreased the level of free radicals, increased autophagy and restored P301L tau-induced impairments in mitophagy. Overall, our findings suggest that spermidine supplementation might represent an attractive therapeutic approach to prevent/counteract tau-related mitochondrial impairments.

Funder

Wilhelm Doerenkamp-Foundation

Novartis Foundation for Medical-Biological Research

Swiss Government Excellence Scholarships

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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