Phosphodiesterases as therapeutic targets for huntington’s disease

Francesca R. Fusco, Carmela Giampà

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)365-377
Number of pages13
JournalCurrent Pharmaceutical Design
Volume21
Issue number3
Publication statusPublished - Jan 1 2015

Fingerprint

Cyclic AMP Response Element-Binding Protein
Huntington Disease
Brain-Derived Neurotrophic Factor
Phosphoric Diester Hydrolases
Phosphodiesterase Inhibitors
Affective Symptoms
Cyclic Nucleotides
Mutant Proteins
Therapeutics
Neurodegenerative Diseases
Psychiatry
Mutation
Pharmaceutical Preparations

Keywords

  • BDNF
  • CAMP
  • CGMP
  • CREB
  • Huntington’s disease
  • Phosphodiesterase inhibitors

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Medicine(all)

Cite this

Phosphodiesterases as therapeutic targets for huntington’s disease. / Fusco, Francesca R.; Giampà, Carmela.

In: Current Pharmaceutical Design, Vol. 21, No. 3, 01.01.2015, p. 365-377.

Research output: Contribution to journalArticle

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