Tiziana Petrozziello (United States of America)
Massachusetts General Hospital
Neurology
Dr. Tiziana Petrozziello is an Instructor in Neurology in Dr. Sadri-Vakili’s laboratory at Massachusetts General Hospital. Her research focuses on unveiling the molecular mechanisms underlying neurodegeneration and neuroinflammation in Amyotrophic Lateral Sclerosis (ALS). Specifically, Dr. Petrozziello is working on elucidating how alterations in mitochondrial function and dynamics led to motor neuron loss in ALS using patient brain samples and biofluids, and how targeting these dysregulated pathways could provide a novel therapeutic approach for the treatment of ALS. Dr. Petrozziello obtained her PhD in Neuroscience at the University of Naples “Federico II” (Naples, Italy) focusing on a novel neuromodulatory role of SOD1 in ALS. Following completion of her PhD she began a post-doctoral fellow in Dr. Annunziato’s laboratory in the Department of Neuroscience at University of Naples “Federico II”, where her studies focused on ionic homeostasis imbalance in ALS. In 2019 she joined Dr. Sadri-Vakili’s laboratory at Massachusetts General Hospital. She has received the Judith and Jean Pape Adams Charitable Foundation and Byrne Family Endowed Fellowship in ALS Research from the Sean M. Healey & AMG Center for ALS at MGH in 2020.

Presenter of 1 Presentation

 Conference Calendar

LOSS OF WWOX AND MUTATIONS IN THE GENE CONTRIBUTE TO MITOCHONDRIAL DYSFUNCTION IN AMYOTROPHIC LATERAL SCLEROSIS

Session Name
0880 - MITOCHONDRIAL DEFECTS IN AD, PD (ID 61)
Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
05:15 PM - 07:15 PM
Room
ONSITE: 133-134
Lecture Time
06:45 PM - 07:00 PM
Presenter

Abstract

Aims

To date, there are no effective treatments for amyotrophic lateral sclerosis (ALS), highlighting the importance of unraveling the mechanisms leading to motor neuron loss. One candidate is the WW domain-containing oxidoreductase (WWOX), widely involved in neurodegeneration.

Methods

Western blots were used to assess the levels of WWOX, and protein involved in the mitochondrial electron transport chain in ALS and control post-mortem motor cortex (mCTX). Project MinE data was assessed to identify genetic variants in WWOX. Cell viability, ATP and reactive oxygen species (ROS) were assessed in SH-SY5Y cells following WWOX knock down using small interfering RNA (siWWOX) or treatment with wild-type and mutant recombinant WWOX proteins. Furthermore, siWWOX was used in a fly model and alterations in behavior were assessed.

Results

WWOX levels were decreased in ALS mCTX and we identified several rare and ALS specific variants in WWOX. Among these variants, the stop codon mutation at amino acid 261 decreased cell viability, reduced ATP levels, and increased ROS in vitro, consistent with decreases in the mitochondrial membrane ATP synthase of complex V and the cytochrome c oxidase of complex IV in ALS mCTX. Furthermore, siWWOX decreased ROS levels in SH-SY5Y cells, suggesting a link between loss of WWOX and increases in oxidative stress in ALS. Similarly, knocking down WWOX in a fly model reduced sleep supporting a pathogenic role for loss of WWOX.

Conclusions

Together, our findings suggest that loss of WWOX or mutations in the gene that lead to a truncated protein exacerbate mitochondrial dysfunction in ALS.

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