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.
Original language | English |
---|---|
Article number | 110822 |
Journal | Food and Chemical Toxicology |
Volume | 134 |
DOIs | |
Publication status | Published - Dec 1 2019 |
Fingerprint
Keywords
- Alzheimer's disease
- cAMP
- cGMP
- Isoform
- Phosphodiesterase
- Subtype
ASJC Scopus subject areas
- Food Science
- Toxicology
Cite this
Phosphodiesterase inhibitors say NO to Alzheimer's disease. / Nabavi, Seyed Mohammad; Talarek, Sylwia; Listos, Joanna; Nabavi, Seyed Fazel; Devi, Kasi Pandima; Roberto de Oliveira, Marcos; Tewari, Devesh; Argüelles, Sandro; Mehrzadi, Saeed; Hosseinzadeh, Azam; D'onofrio, Grazia; Orhan, Ilkay Erdogan; Sureda, Antoni; Xu, Suowen; Momtaz, Saeedeh; Farzaei, Mohammad Hosein.
In: Food and Chemical Toxicology, Vol. 134, 110822, 01.12.2019.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Phosphodiesterase inhibitors say NO to Alzheimer's disease
AU - Nabavi, Seyed Mohammad
AU - Talarek, Sylwia
AU - Listos, Joanna
AU - Nabavi, Seyed Fazel
AU - Devi, Kasi Pandima
AU - Roberto de Oliveira, Marcos
AU - Tewari, Devesh
AU - Argüelles, Sandro
AU - Mehrzadi, Saeed
AU - Hosseinzadeh, Azam
AU - D'onofrio, Grazia
AU - Orhan, Ilkay Erdogan
AU - Sureda, Antoni
AU - Xu, Suowen
AU - Momtaz, Saeedeh
AU - Farzaei, Mohammad Hosein
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - cAMP
KW - cGMP
KW - Isoform
KW - Phosphodiesterase
KW - Subtype
UR - http://www.scopus.com/inward/record.url?scp=85072265292&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072265292&partnerID=8YFLogxK
U2 - 10.1016/j.fct.2019.110822
DO - 10.1016/j.fct.2019.110822
M3 - Review article
AN - SCOPUS:85072265292
VL - 134
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
SN - 0278-6915
M1 - 110822
ER -