DJ-1: A promising therapeutic candidate for ischemia-reperfusion injury

Lazzari, Federica De; Prag, Hiran A.; Gruszczyk, Anja V.; Whitworth, Alexander J.; Bisaglia, Marco

doi:10.1016/j.redox.2021.101884

Cited by 21 publications

(14 citation statements)

References 165 publications

(144 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, our results indicate that the absence of dj-1β affects adult fly survival under oxygen depletion, in line with a purported protective role of DJ-1 against hypoxia injury [ 18 ]. Remarkably, the effects observed in dj-1β knock-out mutants do not seem to rely on the Ccs-dependent Sod1 maturation pathway, as dj-1β knock-out flies showed an accumulation of Sod1 similar to controls.…”

Section: Discussionsupporting

confidence: 80%

See 1 more Smart Citation

DJ-1 and SOD1 Act Independently in the Protection against Anoxia in Drosophila melanogaster

et al. 2022

Self Cite

View full text Add to dashboard Cite

Redox homeostasis is a vital process the maintenance of which is assured by the presence of numerous antioxidant small molecules and enzymes and the alteration of which is involved in many pathologies, including several neurodegenerative disorders. Among the different enzymes involved in the antioxidant response, SOD1 and DJ-1 have both been associated with the pathogenesis of amyotrophic lateral sclerosis and Parkinson’s disease, suggesting a possible interplay in their mechanism of action. Copper deficiency in the SOD1-active site has been proposed as a central determinant in SOD1-related neurodegeneration. SOD1 maturation mainly relies on the presence of the protein copper chaperone for SOD1 (CCS), but a CCS-independent alternative pathway also exists and functions under anaerobic conditions. To explore the possible involvement of DJ-1 in such a pathway in vivo, we exposed Drosophila melanogaster to anoxia and evaluated the effect of DJ-1 on fly survival and SOD1 levels, in the presence or absence of CCS. Loss of DJ-1 negatively affects the fly response to the anoxic treatment, but our data indicate that the protective activity of DJ-1 is independent of SOD1 in Drosophila, indicating that the two proteins may act in different pathways.

show abstract

Section: Discussionsupporting

confidence: 80%

“…DJ-1 is a multifunctional protein implicated in oxidative stress responses, even though its specific role is still controversial [ 17 , 18 , 19 ]. Several different DJ-1 gene mutations have been associated with familial autosomal recessive forms of PD [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

DJ-1 and SOD1 Act Independently in the Protection against Anoxia in Drosophila melanogaster

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Changes in the mitochondrial proteome reflect the balance existing between metabolic adaptation and damage. Amongst the non-metabolic differentially expressed proteins detected in the post-conditioned hearts, both VDAC2 and DJ-1 have been previously related to cardioprotection [53][54][55]. Furthermore, HSPA9, a protein necessary for the mitochondrial import of DJ-1 [56] was also up-regulated.…”

Section: Mitochondrial Response To Post-conditioning In the Pig Heartmentioning

confidence: 99%

Network-Assisted Systems Biology Analysis of the Mitochondrial Proteome in a Pre-Clinical Model of Ischemia, Revascularization and Post-Conditioning

Gallinat

Vilahur

Padró

et al. 2022

IJMS

View full text Add to dashboard Cite

Infarct size is the major risk predictor for developing heart failure after an acute myocardial infarction (AMI). The discovery of the conditioning phenomena (i.e., repetitive brief cycles of ischemia applied either before or after a prolonged ischemic insult) has highlighted the existence of endogenous protective mechanisms of the heart potentially limiting infarct size after revascularization. However, most cardioprotective strategies, aiming at infarct size reduction, have failed in clinical studies. Thus, cardioprotection is an unmet clinical need. In the present study, we took a network-assisted systems biology approach to explore the mitochondrial proteomic signature of the myocardium after ischemia, ischemia with direct revascularization, and ischemia with re-establishment of blood flow by post-conditioning in a swine model of AMI. Furthermore, network extension with the ENCODE project human regulatory data allowed the prediction of potential transcription factors at play in the response to post-conditioning of the myocardium. Collectively, our results identify cardiac metabolism as a driver of cardioprotection, highlighting a dual role for post-conditioning promoting metabolic reprogramming of the myocardium, and a protective response mediated by VDAC2 and DJ-1 in the mitochondria.

show abstract

“…Similarly, lymphoblasts derived from DJ-1 deficient PD patients also exhibit reduced HIF-1α levels. However, DJ-1 knockout has been related to normoxic HIF-1α stabilization in SH-SY5Y cells and MEFs [ 63 , 64 ].…”

Section: Crosstalk Between Hypoxia Hif-1α and Pd Related Genesmentioning

confidence: 99%

Hypoxia Signaling in Parkinson’s Disease: There Is Use in Asking “What HIF?”

Pinilla

Ugun-Klusek

Rutella

et al. 2021

Biology

View full text Add to dashboard Cite

Hypoxia is a condition characterized by insufficient tissue oxygenation, which results in impaired oxidative energy production. A reduction in cellular oxygen levels induces the stabilization of hypoxia inducible factor α (HIF-1α), master regulator of the molecular response to hypoxia, involved in maintaining cellular homeostasis and driving hypoxic adaptation through the control of gene expression. Due to its high energy requirement, the brain is particularly vulnerable to oxygen shortage. Thus, hypoxic injury can cause significant metabolic changes in neural cell populations, which are associated with neurodegeneration. Recent evidence suggests that regulating HIF-1α may ameliorate the cellular damage in neurodegenerative diseases. Indeed, the hypoxia/HIF-1α signaling pathway has been associated to several processes linked to Parkinson’s disease (PD) including gene mutations, risk factors and molecular pathways such as mitochondrial dysfunction, oxidative stress and protein degradation impairment. This review will explore the impact of hypoxia and HIF-1α signaling on these specific molecular pathways that influence PD development and will evaluate different novel neuroprotective strategies involving HIF-1α stabilization.

show abstract

DJ-1: A promising therapeutic candidate for ischemia-reperfusion injury

Cited by 21 publications

References 165 publications

DJ-1 and SOD1 Act Independently in the Protection against Anoxia in Drosophila melanogaster

DJ-1 and SOD1 Act Independently in the Protection against Anoxia in Drosophila melanogaster

Network-Assisted Systems Biology Analysis of the Mitochondrial Proteome in a Pre-Clinical Model of Ischemia, Revascularization and Post-Conditioning

Hypoxia Signaling in Parkinson’s Disease: There Is Use in Asking “What HIF?”

Contact Info

Product

Resources

About