Phosphodiesterase inhibitors say NO to Alzheimer's disease

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 -