Cathepsin-dependent neuronal death pathways induced by methylmercury

Hiroshi Nakanishi, Hiro Take

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

An intoxication of methylmercury (MeHg), also known as Minamata disease, commonly results from the ingestion of MeHg-contaminated food. MeHg is easily absorbed from the intestine and therefore if transported to the central nervous system (CNS) through the blood-brain barrier. Among CNS neurons, the cerebellar granule neurons are especially vulnerable to MeHg intoxication. Exposure to MeHg during development results in an impaired migration of the cerebellar granule neurons and impaired synaptogenesis, thus leading to a disordering of the cerebellar architecture. On the other hand, exposure to MeHg during adulthood can also result in loss of cerebellar granule neurons from the internal granule cell layer, while Purkinje cells remain intact. MeHg has been also reported to affect functions of astrocytes and microglia. Despite the clinical importance, the understanding of the mechanism underlying MeHg-induced neuronal death is still limited. Cathepsins B and D, two major lysosomal proteases in the CNS, have been implicated in neuronal death.Cathepsins B and D are involved in neuronal death through different two pathways: intracellular proteolysis after their leakage from the lysosome to the cytosol of neurons and extracellular proteolysis after secreted from activated microglia.Here, we summarize possible neuronal and microglial cathepsin-dependent neuronal death pathways induced by various stimuli including MeHg, and then the potential application of inhibitors for cathepsins on MeHg-induced pathological changes in the CNS.

Original languageEnglish
Title of host publicationMethylmercury
Subtitle of host publicationFormation, Sources and Health Effects
PublisherNova Science Publishers, Inc.
Pages81-95
Number of pages15
ISBN (Print)9781617618383
Publication statusPublished - Feb 1 2011

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All Science Journal Classification (ASJC) codes

  • Environmental Science(all)

Cite this

Nakanishi, H., & Take, H. (2011). Cathepsin-dependent neuronal death pathways induced by methylmercury. In Methylmercury: Formation, Sources and Health Effects (pp. 81-95). Nova Science Publishers, Inc..