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Role of neuronal signaling effector hydrogen sulfide (H 2 S) and sulfhydration in Huntington's disease
Author(s) -
Paul Bindu Diana,
Snyder Solomon H.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1271.6
Subject(s) - neurodegeneration , huntingtin , cystathionine beta synthase , huntington's disease , chemistry , microbiology and biotechnology , transsulfuration , sulfurtransferase , huntingtin protein , biochemistry , biology , neuroscience , mutant , cysteine , medicine , disease , gene , enzyme
Hydrogen sulfide (H 2 S) has joined the ranks of the gasotransmitters, nitric oxide and carbon monoxide as a signaling molecule that modulates a wide spectrum of physiological processes. H 2 S signals via sulfhydration, wherein it mediates the conversion of −SH groups of reactive cysteine residues on target proteins to −SSH or persulfide groups. H 2 S is synthesized by cystathionine gamma lyase (CSE), cystathionine beta synthase (CBS) and 3‐mercaptopyruvate sulfurtransferase of the reverse transsulfuration pathway. Aberrant H 2 S metabolism is involved in the progressive neurodegeneration seen in Huntington's disease (HD). HD is a devastating condition and is currently considered to be an incurable disease of the nervous system. New treatment options are highly sought after. We asked how normal healthy neural development is influenced by the differential interplay of huntingtin versus mutant huntingtin (mHtt) function vis‐à‐vis CSE and CBS action in the nervous system. Specifically, we sought to understand how the modalities of mutant transformation of huntingtin at the genetic and epigenetic levels affect mHtt effects on H 2 S action. We chose cell culture and mouse models of HD to study their manifestation on the progressive neurodegeneration observed alongside the cognitive and motor deficits that are characteristic of human HD patients. We have shown that loss of CSE mediates neurodegeneration and disease progression in HD. It appears that the neuronal redox effector functions of H 2 S are differentially modulated by the action of mHtt on CSE and CBS thereby affecting disease progression in HD by variable regulatory mechanisms. Representative Recognition/Honor ASBMB/ jbc Herbert Tabor Young Investigator Award (May 2015) at the third European Conference on the Biology of Hydrogen Sulfide at Athens, Greece. Support or Funding Information United States Public Health Service Grant MH18501 to S.H.S, CHDI Foundation