A Study of Glutathione S-transferase pi Expression in Central Nervous System of Subjects with Amyotrophic Lateral Sclerosis Using RNA Extraction from Formalin-Fixed, Paraffin-Embedded Material

Usarek, Ewa; Gajewska, Beata; Kaźmierczak, Beata; Kuźma, Monika; Dziewulska, Dorota; Barańczyk‐Kuźma, Anna

doi:10.1007/s11064-005-6771-1

Cited by 19 publications

(12 citation statements)

References 21 publications

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“…Studies of GPx activities in erythrocyte samples from ALS patients have given mixed results with some showing significant diminution while others showed no change [165,166], analogous to the situation described for HD (above). Another study reported that mRNA levels for GST pi were significantly down regulated in the spinal cord, motor cortex, and the sensory cortex of ALS patients [114]. Furthermore a cohort of patients with a unique haplotype signature in the glutathione synthase gene was found to correlate with ALS patients who had exposures to metals and chemical solvents [167].…”

Section: Impairment Of Glutathione Homeostasis In Neurodegeneratimentioning

confidence: 99%

Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases

2012

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Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are increasingly implicated in the induction and progression of neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, and Friedreich’s ataxia. In this review background is provided on the steady-state synthesis, regulation, and transport of glutathione, with primary focus on the brain. A brief overview is presented on the distinct but vital roles of glutathione in cellular maintenance and survival, and on the functions of key glutathione-dependent enzymes. Major contributors to initiation and progression of neurodegenerative diseases are considered, including oxidative stress, protein misfolding, and protein aggregation. In each case examples of key regulatory mechanisms are identified that are sensitive to changes in glutathione redox status and/or in the activities of glutathione-dependent enzymes. Mechanisms of dysregulation of glutathione and/or glutathione-dependent enzymes are discussed that are implicated in pathogenesis of each neurodegenerative disease. Limitations in information or interpretation are identified, and possible avenues for further research are described with an aim to elucidating novel targets for therapeutic interventions. The pros and cons of administration of N-acetylcysteine or glutathione as therapeutic agents for neurodegenerative diseases, as well as the potential utility of serum glutathione as a biomarker, are critically evaluated.

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Section: Impairment Of Glutathione Homeostasis In Neurodegeneratimentioning

confidence: 99%

Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases

2012

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“…These changes correlate with the disease progression. The spinal cord tissues obtained postmortem from patients with ALS showed increased protein glutathionylation in the gray matter [168] and reduced GST mRNA expression [169] compared to age-matched controls. Loss of GLT-1 has been reported in the spinal cord and motor cortex of ALS patients [170,171].…”

Section: Disorders Of Gsh Metabolism In Neurodegenerative Diseasementioning

confidence: 99%

Impaired Glutathione Synthesis in Neurodegeneration

Aoyama

Nakaki

2013

IJMS

185

136

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Glutathione (GSH) was discovered in yeast cells in 1888. Studies of GSH in mammalian cells before the 1980s focused exclusively on its function for the detoxication of xenobiotics or for drug metabolism in the liver, in which GSH is present at its highest concentration in the body. Increasing evidence has demonstrated other important roles of GSH in the brain, not only for the detoxication of xenobiotics but also for antioxidant defense and the regulation of intracellular redox homeostasis. GSH also regulates cell signaling, protein function, gene expression, and cell differentiation/proliferation in the brain. Clinically, inborn errors in GSH-related enzymes are very rare, but disorders of GSH metabolism are common in major neurodegenerative diseases showing GSH depletion and increased levels of oxidative stress in the brain. GSH depletion would precipitate oxidative damage in the brain, leading to neurodegenerative diseases. This review focuses on the significance of GSH function, the synthesis of GSH and its metabolism, and clinical disorders of GSH metabolism. A potential approach to increase brain GSH levels against neurodegeneration is also discussed.

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“…Notably, impairment in defensive mechanisms has also been revealed in ALS, including downregulation of members of glutathione S-transferase family [54, 55], peroxiredoxins [56], and, in particular, the transcriptional factor Nrf2 [57–60]. …”

Section: Amyotrophic Lateral Sclerosis (Als)mentioning

confidence: 99%

SOD1 and DJ-1 Converge at Nrf2 Pathway: A Clue for Antioxidant Therapeutic Potential in Neurodegeneration

Milani

Ambrosi

Gammoh

et al. 2013

Oxidative Medicine and Cellular Longevity

105

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Neurodegenerative diseases share diverse pathological features and among these oxidative stress (OS) plays a leading role. Impaired activity and reduced expression of antioxidant proteins have been reported as common events in several aging-associated disorders. In this review paper, we first provide an overview of the involvement of reactive oxygen species- (ROS-) induced oxidative damage in Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Subsequently, we focus on DJ-1 and SOD1 proteins, which are involved in PD and ALS and also exert a prominent role in the interaction between redox homeostasis and neurodegeneration. Interestingly, recent studies demonstrated that DJ-1 and SOD1 are both tightly connected with Nrf2 protein, a transcriptional factor and master regulator of the expression of many antioxidant/detoxification genes. Nrf2 is emerging as a key neuroprotective protein in neurodegenerative diseases, since it helps neuronal cells to cope with toxic insults and OS. We herein summarize the recent literature providing a detailed picture of the promising therapeutic efficacy of Nrf2 natural and synthetic inducers as disease-modifying molecules for the treatment of neurodegenerative diseases.

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A Study of Glutathione S-transferase pi Expression in Central Nervous System of Subjects with Amyotrophic Lateral Sclerosis Using RNA Extraction from Formalin-Fixed, Paraffin-Embedded Material

Cited by 19 publications

References 21 publications

Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases

Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases

Impaired Glutathione Synthesis in Neurodegeneration

SOD1 and DJ-1 Converge at Nrf2 Pathway: A Clue for Antioxidant Therapeutic Potential in Neurodegeneration

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