PMID- 25159076
OWN - NLM
STAT- MEDLINE
DCOM- 20150728
LR  - 20190728
IS  - 1873-4286 (Electronic)
IS  - 1381-6128 (Linking)
VI  - 21
IP  - 3
DP  - 2015
TI  - Phosphodiesterases as therapeutic targets for Huntington's disease.
PG  - 365-77
AB  - Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative 
      disorder characterized by motor dysfunction, cognitive decline, and emotional and 
      psychiatric disturbances. The genetic mutation is characterized by a CAG 
      expansion, resulting in the formation of a mutant huntingtin protein with an 
      expanded polyglutamine repeat region. Mutated huntingtin has been shown to impair 
      a number of physiological activities by interacting with several factors. In 
      particular, cAMP response element-binding protein (CREB) and brain-derived 
      neurotrophic factor (BDNF) are severely affected by mutant huntingtin. In this 
      view, drugs targeted at counteracting CREB loss of function and BDNF decrease 
      have been considered as powerful tools to treat HD. Recently, cyclic nucleotide 
      phosphodiesterase (PDE) inhibitors have been used successfully to increase levels 
      of CREB and BDNF in HD models. Indeed, PDE4, 5 or 10 inhibitors have been shown 
      to afford neuroprotection and modulation of CREB and BDNF. In this review, we 
      will summarize the data supporting the use of PDE inhibitors as the therapeutical 
      approach to fight HD and we will discuss the possible mechanisms of action 
      underlying these effects.
FAU - Fusco, Francesca R
AU  - Fusco FR
FAU - Giampa, Carmela
AU  - Giampa C
AD  - Laboratory of Neuroanatomy, Santa Lucia Foundation IRCCS at the European Center 
      for Brain Research, via del Fosso Fiorano 64, 00143 Rome. f.fusco@hsantalucia.it.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Pharm Des
JT  - Current pharmaceutical design
JID - 9602487
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - EC 3.1.4.- (Phosphoric Diester Hydrolases)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Huntington Disease/*drug therapy/*enzymology
MH  - Phosphodiesterase Inhibitors/*therapeutic use
MH  - Phosphoric Diester Hydrolases/*chemistry
EDAT- 2014/08/28 06:00
MHDA- 2015/07/29 06:00
CRDT- 2014/08/28 06:00
PHST- 2014/04/02 00:00 [received]
PHST- 2014/08/25 00:00 [accepted]
PHST- 2014/08/28 06:00 [entrez]
PHST- 2014/08/28 06:00 [pubmed]
PHST- 2015/07/29 06:00 [medline]
AID - CPD-EPUB-61969 [pii]
AID - 10.2174/1381612820666140826113957 [doi]
PST - ppublish
SO  - Curr Pharm Des. 2015;21(3):365-77. doi: 10.2174/1381612820666140826113957.