Role of transcription factor yin yang 1 in manganese-induced reduction of astrocytic glutamate transporters: Putative mechanism for manganese-induced neurotoxicity

Pratap Karki, Keisha Smith, James Johnson, Michael Aschner, Eunsook Lee

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Astrocytes are the most abundant non-neuronal glial cells in the brain. Once relegated to a mere supportive role for neurons, contemporary dogmas ascribe multiple active roles for these cells in central nervous system (CNS) function, including maintenance of optimal glutamate levels in synapses. Regulation of glutamate levels in the synaptic cleft is crucial for preventing excitotoxic neuronal injury. Glutamate levels are regulated predominantly by two astrocytic glutamate transporters, glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST). Indeed, the dysregulation of these transporters has been linked to several neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD), as well as manganism, which is caused by overexposure to the trace metal, manganese (Mn). Although Mn is an essential trace element, its excessive accumulation in the brain as a result of chronic occupational or environmental exposures induces a neurological disorder referred to as manganism, which shares common pathological features with Parkinsonism. Mn decreases the expression and function of both GLAST and GLT-1. Astrocytes are commonly targeted by Mn, and thus reduction in astrocytic glutamate transporter function represents a critical mechanism of Mn-induced neurotoxicity. In this review, we will discuss the role of astrocytic glutamate transporters in neurodegenerative diseases and Mn-induced neurotoxicity.

Original languageEnglish (US)
Article number3618
Pages (from-to)53-59
Number of pages7
JournalNeurochemistry International
Volume88
DOIs
StatePublished - Sep 1 2015

Fingerprint

Yin-Yang
Amino Acid Transport System X-AG
Manganese
Transcription Factors
Glutamic Acid
Astrocytes
Neurodegenerative Diseases
Environmental Exposure
Amyotrophic Lateral Sclerosis
Brain
Trace Elements
Parkinsonian Disorders
Occupational Exposure
Nervous System Diseases
Neuroglia
Synapses
Parkinson Disease
Alzheimer Disease
Central Nervous System
Metals

Keywords

  • Astrocytes
  • GLAST
  • GLT-1
  • Glutamate
  • Manganese
  • Neurotoxicity

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Role of transcription factor yin yang 1 in manganese-induced reduction of astrocytic glutamate transporters : Putative mechanism for manganese-induced neurotoxicity. / Karki, Pratap; Smith, Keisha; Johnson, James; Aschner, Michael; Lee, Eunsook.

In: Neurochemistry International, Vol. 88, 3618, 01.09.2015, p. 53-59.

Research output: Contribution to journalArticle

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