Oxidative stress biomarkers in sporadic ALS

Mitsumoto, Hiroshi; Santella, Regina M.; Liu, Xinhua; Богданов, М. Б.; Zipprich, Jennifer; Wu, Hui‐Chen; Mahata, Julie; Kilty, M; Bednarz, Kate; Bell, Daniel; Gordon, Paul H.; Hornig, Mady; Mehrazin, Mahsa; Naini, Ali; Beal, M. Flint; Factor-Litvak, Pam

doi:10.1080/17482960801933942

Cited by 143 publications

(92 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The change in urine levels of 8OH2'dG were negatively correlated with the rate of change of ALSFRS-R scores, suggesting that 8OH2'dG could serve as a potential prognostic marker, and also confirms that oxidative stress contributes to the ALS pathology. Similar observations were shown in another study using patients with sALS; however, no trend was observed between 8OH2'dG levels and ALSFRS-R scores [156]. Taken together, these results demonstrate the potential utility of urine for ALS biomarker discovery.…”

Section: Biomarkers In Urinesupporting

confidence: 88%

“…To the best of our knowledge, only neurotrophin receptor p75 (p75NTR) [152], glucosylgalactosyl hydroxylysine (GluGal Hyl) [153], type IV collagen [154], and 8-hydroxyl-2'-deoxyguanosin (8OH2'dG) [155,156] have been explored as potential biomarkers warranting further studies of urine for ALS biomarkers. Recently, the extracellular domain of p75NTR, which is a regulator of cell survival and death, was shown to exhibit increased levels in urine from ALS patients with limb or bulbar onset as compared with healthy controls [152].…”

Section: Biomarkers In Urinementioning

confidence: 99%

See 1 more Smart Citation

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

Bowser

2017

Neurotherapeutics

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a highly heterogeneous disease with no effective treatment. Drug development has been hampered by the lack of biomarkers that aid in early diagnosis, demonstrate target engagement, monitor disease progression, and can serve as surrogate endpoints to assess the efficacy of treatments. Fluid-based biomarkers may potentially address these issues. An ideal biomarker should exhibit high specificity and sensitivity for distinguishing ALS from control (appropriate disease mimics and other neurologic diseases) populations and monitor disease progression within individual patients. Significant progress has been made using cerebrospinal fluid, serum, and plasma in the search for ALS biomarkers, with urine and saliva biomarkers still in earlier stages of development. A few of these biomarker candidates have demonstrated use in patient stratification, predicting disease course (fast vs slow progression) and severity, or have been used in preclinical and clinical applications. However, while ALS biomarker discovery has seen tremendous advancements in the last decade, validating biomarkers and moving them towards the clinic remains more elusive. In this review, we highlight biomarkers that are moving towards clinical utility and the challenges that remain in order to implement biomarkers at all stages of the ALS drug development process.

show abstract

Section: Biomarkers In Urinesupporting

confidence: 88%

Section: Biomarkers In Urinementioning

confidence: 99%

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

Bowser

2017

Neurotherapeutics

View full text Add to dashboard Cite

show abstract

“…Signs of oxidative stress are observed in ALS rodent models and in ALS patients, such as 8-oxodeoxyguanosine (8-oxodG), urinary 15-F(2t)-isoprostane, protein carbonylation, and markers of lipid peroxidation [5,7,104,106]. The most studied form of ALS is a familial ALS (FALS) in which the antioxidant enzyme SOD1 is mutated (SOD1 G93A ).…”

Section: Beneficial Effect Of Nox Inhibition: Potential Cns Indicationsmentioning

confidence: 99%

Targeting NOX enzymes in the central nervous system: therapeutic opportunities

Sorce

Krause

Jaquet

2012

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Among the pathogenic mechanisms underlying central nervous system (CNS) diseases, oxidative stress is almost invariably described. For this reason, numerous attempts have been made to decrease reactive oxygen species (ROS) with the administration of antioxidants as potential therapies for CNS disorders. However, such treatments have always failed in clinical trials. Targeting specific sources of reactive oxygen species in the CNS (e.g. NOX enzymes) represents an alternative promising option. Indeed, NOX enzymes are major generators of ROS, which regulate progression of CNS disorders as diverse as amyotrophic lateral sclerosis, schizophrenia, Alzheimer disease, Parkinson disease, and stroke. On the other hand, in autoimmune demyelinating diseases, ROS generated by NOX enzymes are protective, presumably by dampening the specific immune response. In this review, we discuss the possibility of developing therapeutics targeting NADPH oxidase (NOX) enzymes for the treatment of different CNS pathologies. Specific compounds able to modulate the activation of NOX enzymes, and the consequent production of ROS, could fill the need for disease-modifying drugs for many incurable CNS pathologies.

show abstract

“…Raised levels of thiobarbituric acid reactive substances (TBARS) and advanced oxidation protein products (AOPP) and decreased ferric-reducing ability of plasma (FRAP) were detected in the plasma or erythrocytes of SALS patients [44][45][46], but plasma protein carbonyl (PC) levels surprisingly did not differ between SALS patients and control subjects [16]. More conclusive results came from a study where urine from SALS patients contained a higher level of isoprostanoids (IsoPs) and 8-OHdG compared to a control group [16,47], suggesting that IsoPs and 8-OHdG could be considered markers of OS in ALS. These studies included only 50 participants with SALS compared to 46 control subjects.…”

Section: Clinical Studies Os Biomarkersmentioning

confidence: 99%