PMID- 16604191
OWN - NLM
STAT- MEDLINE
DCOM- 20060614
LR  - 20211020
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 116
IP  - 5
DP  - 2006 May
TI  - Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via 
      HSJ1b and transglutaminase.
PG  - 1410-24
AB  - There is no treatment for the neurodegenerative disorder Huntington disease (HD). 
      Cystamine is a candidate drug; however, the mechanisms by which it operates 
      remain unclear. We show here that cystamine increases levels of the heat shock 
      DnaJ-containing protein 1b (HSJ1b) that are low in HD patients. HSJ1b inhibits 
      polyQ-huntingtin-induced death of striatal neurons and neuronal dysfunction in 
      Caenorhabditis elegans. This neuroprotective effect involves stimulation of the 
      secretory pathway through formation of clathrin-coated vesicles containing 
      brain-derived neurotrophic factor (BDNF). Cystamine increases BDNF secretion from 
      the Golgi region that is blocked by reducing HSJ1b levels or by overexpressing 
      transglutaminase. We demonstrate that cysteamine, the FDA-approved reduced form 
      of cystamine, is neuroprotective in HD mice by increasing BDNF levels in brain. 
      Finally, cysteamine increases serum levels of BDNF in mouse and primate models of 
      HD. Therefore, cysteamine is a potential treatment for HD, and serum BDNF levels 
      can be used as a biomarker for drug efficacy.
FAU - Borrell-Pages, Maria
AU  - Borrell-Pages M
AD  - Institut Curie, CNRS UMR 146, Orsay, France.
FAU - Canals, Josep M
AU  - Canals JM
FAU - Cordelieres, Fabrice P
AU  - Cordelieres FP
FAU - Parker, J Alex
AU  - Parker JA
FAU - Pineda, Jose R
AU  - Pineda JR
FAU - Grange, Ghislaine
AU  - Grange G
FAU - Bryson, Elzbieta A
AU  - Bryson EA
FAU - Guillermier, Martine
AU  - Guillermier M
FAU - Hirsch, Etienne
AU  - Hirsch E
FAU - Hantraye, Philippe
AU  - Hantraye P
FAU - Cheetham, Michael E
AU  - Cheetham ME
FAU - Neri, Christian
AU  - Neri C
FAU - Alberch, Jordi
AU  - Alberch J
FAU - Brouillet, Emmanuel
AU  - Brouillet E
FAU - Saudou, Frederic
AU  - Saudou F
FAU - Humbert, Sandrine
AU  - Humbert S
LA  - eng
GR  - G0401350/MRC_/Medical Research Council/United Kingdom
GR  - MH/NS 31862/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060406
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (DNAJB2 protein, human)
RN  - 0 (HSP40 Heat-Shock Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Neuroprotective Agents)
RN  - 5UX2SD1KE2 (Cysteamine)
RN  - EC 2.3.2.13 (Transglutaminases)
RN  - R110LV8L02 (Cystamine)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Brain/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis
MH  - Caenorhabditis elegans
MH  - Cystamine/*chemistry/*metabolism
MH  - Cysteamine/*chemistry
MH  - HSP40 Heat-Shock Proteins/*physiology
MH  - Humans
MH  - Huntington Disease/*metabolism
MH  - Macaca
MH  - Mice
MH  - Mice, Transgenic
MH  - Middle Aged
MH  - Molecular Chaperones/*physiology
MH  - Neuroprotective Agents/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transglutaminases/*metabolism
PMC - PMC1430359
EDAT- 2006/04/11 09:00
MHDA- 2006/06/15 09:00
PMCR- 2006/05/01
CRDT- 2006/04/11 09:00
PHST- 2005/12/07 00:00 [received]
PHST- 2006/02/14 00:00 [accepted]
PHST- 2006/04/11 09:00 [pubmed]
PHST- 2006/06/15 09:00 [medline]
PHST- 2006/04/11 09:00 [entrez]
PHST- 2006/05/01 00:00 [pmc-release]
AID - 27607 [pii]
AID - 10.1172/JCI27607 [doi]
PST - ppublish
SO  - J Clin Invest. 2006 May;116(5):1410-24. doi: 10.1172/JCI27607. Epub 2006 Apr 6.