Role of Glutathione-S-transferases in neurological problems

ABSTRACT

Introduction: Role of Glutathione-S-transferases (GSTs) has been well explored in the cellular detoxification process, regulation of redox homeostasis and S-glutothionylation of target proteins like JNK, ASK1 etc. However, altered levels or functions of this enzyme or their subtypes have emerged in the development of several pathologies diseases such as Alzheimer’s disease, Parkinson’s disease, cancer and related conditions. Oxidative stress is one of the possible pathological events that contributes significantly to activation of degenerating cascades inside neuronal cells. The central nervous system is highly sensitive to oxidative stress because of low levels or capacities of antioxidant enzymes. The brain is highly metabolic in nature making it susceptible to oxidative stress.

Areas covered: The present review provides a comprehensive overview of the multiple connections of GSTs within diverse neurological diseases including cancer. Furthermore, the authors have made significant efforts to discuss the regulation of different GST isoforms that have been associated with various pathological processes such as glioblastoma, Alzheimer’s disease, Parkinson’s disease, stroke and epilepsy.

Expert opinion: Though GSTs have been one of the key areas of scientific research over the last few decades, much remains to be elucidated about their physiological functions as well as pathological involvement of GSTs and their polymorphic variants.

KEYWORDS:

• GST
• neurological disease
• oxidative stress
• polymorphism

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Corrigendum

Article highlights

• Glutathione-S-transferases are known to be involved in the cellular detoxification process as well as regulation of cellular redox homeostasis.

• Central nervous system is highly sensitive to oxidative stress because of low antioxidant enzymes and high oxygen levels.

• Dysregulation of GSTs expression might be associated with various pathological processes such as Alzheimer’s disease, Parkinson’s disease, stroke etc.

• Many pharmaceutical companies received a number of patents for various GST inhibitors,few of which are available in the form of drugs.

• A significant correlation between GSTs and the genesis of anticancer drug resistance has been established.

• Scope of GST modulators as a next generation drugs to deal with drug resistance, cancer as well as neurological and neurodegenerative diseases.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The authors would like to thank the financial support of Council of Scientific and Industrial Research [09/135/705/2014-EMR-I], Department of Science & Technology [DST/INSPIRE Fellowship/2014/IF 140742] and UGC, New Delhi, India, for carrying out this work.