Molecular and Physiological Determinants of Amyotrophic Lateral Sclerosis: What the DJ-1 Protein Teaches Us
<p>The physiological functions of DJ-1 possibly affected in ALS pathology. DJ-1 participates in the maintenance of mitochondrial and cellular redox homeostasis. These functions are fundamental to sustaining the high energetic demand of MNs without producing excessive levels of ROS, and collectively, they contribute to MNs’ healthiness (<b>on the left</b>). Alterations in DJ-1 physiological functions might affect mitochondria functionality, reducing the levels of ATP below MNs’ needs. At the same time, mitochondria dysfunctions might promote increased levels of ROS. Altogether, these alterations might constitute a pathological background enhancing the probability of developing ALS (<b>on the right</b>) (created with BioRender.com, accessed on 6 April 2023).</p> "> Figure 2
<p>DJ-1-mediated protection against hypoxia. Under normoxia conditions, HIF-1α is constantly hydroxylated, ubiquitinated, and degraded at the proteasome. Under hypoxic conditions, HIF-1α translocates into the nucleus, where it promotes the expression of numerous genes involved in hypoxic adaptation. Among them, the VEGF protein stimulates vessel growth and promotes the survival of motor neurons during hypoxia. DJ-1 has been proposed to act as a negative regulator of VHL stabilizing the transcription factor HIF-1α. Acronyms are mentioned in the main text. (Created with BioRender.com, accessed on 6 April 2023.)</p> ">
Abstract
:1. Introduction
2. DJ-1 Protection against Oxidative Stress and Mitochondrial Dysfunction: Implications for ALS
3. DJ-1 Involvement in Energy Metabolism: Implications for ALS
4. DJ-1 Involvement in Hypoxia Response: Implications for ALS
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Sandrelli, F.; Bisaglia, M. Molecular and Physiological Determinants of Amyotrophic Lateral Sclerosis: What the DJ-1 Protein Teaches Us. Int. J. Mol. Sci. 2023, 24, 7674. https://doi.org/10.3390/ijms24087674
Sandrelli F, Bisaglia M. Molecular and Physiological Determinants of Amyotrophic Lateral Sclerosis: What the DJ-1 Protein Teaches Us. International Journal of Molecular Sciences. 2023; 24(8):7674. https://doi.org/10.3390/ijms24087674
Chicago/Turabian StyleSandrelli, Federica, and Marco Bisaglia. 2023. "Molecular and Physiological Determinants of Amyotrophic Lateral Sclerosis: What the DJ-1 Protein Teaches Us" International Journal of Molecular Sciences 24, no. 8: 7674. https://doi.org/10.3390/ijms24087674