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Phosphodiesterase Inhibitors Say No to Alzheimer's Disease Publisher Pubmed



Nabavi SM1 ; Talarek S2 ; Listos J2 ; Nabavi SF1 ; Devi KP3 ; Roberto De Oliveira M4 ; Tewari D5 ; Arguelles S6 ; Mehrzadi S7 ; Hosseinzadeh A7 ; Donofrio G8 ; Orhan IE9 ; Sureda A10 ; Xu S11 Show All Authors
Authors
  1. Nabavi SM1
  2. Talarek S2
  3. Listos J2
  4. Nabavi SF1
  5. Devi KP3
  6. Roberto De Oliveira M4
  7. Tewari D5
  8. Arguelles S6
  9. Mehrzadi S7
  10. Hosseinzadeh A7
  11. Donofrio G8
  12. Orhan IE9
  13. Sureda A10
  14. Xu S11
  15. Momtaz S12, 13
  16. Farzaei MH14
Show Affiliations
Authors Affiliations
  1. 1. Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4a St, Lublin, 20-093, Poland
  3. 3. Department of Biotechnology, Alagappa University, Karaikudi, 630003, Tamil Nadu, India
  4. 4. Departamento de Quimica (DQ), Instituto de Ciencias Exatas e da Terra (ICET), Universidade Federal de Mato Grosso (UFMT), Cuiaba, Brazil
  5. 5. Department of Pharmacognosy, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 144411, Punjab, India
  6. 6. Department of Physiology, Faculty of Pharmacy, University of Seville, Seville, Spain
  7. 7. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
  8. 8. Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, IRCCS “Casa Sollievo della Sofferenza�, Viale Cappuccini 1, San Giovanni Rotondo, 71013, FG, Italy
  9. 9. Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Ankara, 06330, Turkey
  10. 10. Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands, CIBEROBN (Physiopathology of Obesity and Nutrition), Palma de Mallorca, Balearic Islands, E-07122, Spain
  11. 11. Aab Cardiovascular Research Institute, University of Rochester, Rochester, 14623, NY, United States
  12. 12. Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran
  13. 13. Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
  14. 14. Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

Source: Food and Chemical Toxicology Published:2019


Abstract

Phosphodiesterases (PDEs) consisted of 11 subtypes (PDE1 to PDE11) and over 40 isoforms that regulate levels of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), the second messengers in cell functions. PDE inhibitors (PDEIs) have been attractive therapeutic targets due to their involvement in diverse medical conditions, e.g. cardiovascular diseases, autoimmune diseases, Alzheimer's disease (AD), etc. Among them; AD with a complex pathology is a progressive neurodegenerative disorder which affect mostly senile people in the world and only symptomatic treatment particularly using cholinesterase inhibitors in clinic is available at the moment for AD. Consequently, novel treatment strategies towards AD are still searched extensively. Since PDEs are broadly expressed in the brain, PDEIs are considered to modulate neurodegenerative conditions through regulating cAMP and cGMP in the brain. In this sense, several synthetic or natural molecules inhibiting various PDE subtypes such as rolipram and roflumilast (PDE4 inhibitors), vinpocetine (PDE1 inhibitor), cilostazol and milrinone (PDE3 inhibitors), sildenafil and tadalafil (PDE5 inhibitors), etc have been reported showing encouraging results for the treatment of AD. In this review, PDE superfamily will be scrutinized from the view point of structural features, isoforms, functions and pharmacology particularly attributed to PDEs as target for AD therapy. © 2019 Elsevier Ltd
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