Hexokinase I N-terminal Based Peptide Prevents the VDAC1-SOD1 G93A Interaction and Re-establishes ALS Cell Viability

Overview

Journal Sci Rep

Specialty Science

Date 2016 Oct 11

PMID 27721436

Citations 37

Authors

Andrea Magri

Ramona Belfiore

Simona Reina

Marianna Flora Tomasello

Maria Carmela Di Rosa

Francesca Guarino

Loredana Leggio

Vito De Pinto

Angela Messina

Affiliations

Soon will be listed here.

Abstract

Superoxide Dismutase 1 mutants associate with 20-25% of familial Amyotrophic Lateral Sclerosis (ALS) cases, producing toxic aggregates on mitochondria, notably in spinal cord. The Voltage Dependent Anion Channel isoform 1 (VDAC1) in the outer mitochondrial membrane is a docking site for SOD1 G93A mutant in ALS mice and the physiological receptor of Hexokinase I (HK1), which is poorly expressed in mouse spinal cord. Our results demonstrate that HK1 competes with SOD1 G93A for binding VDAC1, suggesting that in ALS spinal cord the available HK1-binding sites could be used by SOD1 mutants for docking mitochondria, producing thus organelle dysfunction. We tested this model by studying the action of a HK1-N-terminal based peptide (NHK1). This NHK1 peptide specifically interacts with VDAC1, inhibits the SOD1 G93A binding to mitochondria and restores the viability of ALS model NSC34 cells. Altogether, our results suggest that NHK1 peptide could be developed as a therapeutic tool in ALS, predicting an effective role also in other proteinopathies.

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