4th International Conference on Neurology and Brain Disorders

September 09-11, 2021

September 09 -11, 2021 | Virtual Event
INBC 2021

Roberto Menicagli

Speaker at Neurology and Brain Disorders 2021 - Roberto Menicagli
University of Pavia, Italy
Title : The theoretical possible employ of inhibitor of PDE-5 in Alzheimers’s disease


Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive loss of neurons.. Recent studies indicate that before the AD ,emerges a process of hypometabolism with a simultaneous reduction of the autophagy  ;this  fact promotes the  increase of urea in brain This study aims to demonstrate how the administration of PDE-5 inhibitor compounds can counteract this process
Methods Study in Human Metabolome Data Base of the main pathways of arginine degradation in the relationship of urea and the NO cicles for the analysis of enzyme equilibria
Results. Arginine  produces   urea by arginase and NO by the NO synthase,(NOS.) .The NO  is fundamental for neuronal activity. These meatabolic pathways are dependent by numerous epigenetic factors Aging causes alterations in phosphorylation and inhibit  eNOS . Other pathological conditions are responsible to alterate the  mitochondrial’s function. Oxidative stress  can accelerate the degradation of NO and meanwhile  increase the transformation of arginine into urea
Discussion. The bibliographic study  showed  that for example in diabetes that  is strongly correlated to the onset of Alzheimer ,this disease  favors the presence   of endoproducts of advanced glycosylation (AGE) which can also interrupt the activation of eNOS, as with the formation of N-acetylglucosamine adducts (OGIcNAc) with sites of phosphorylation of serine on eNOS. Under these conditions arginine is therefore more easily converted to urea and at the same time it increases its mitochondrial availability towards other metabolic pathways principally the enhancement of  the activation state of mTOR with consequent inhibition of the autophagy process. To administrate  PDE inhibitors -5, prevents cGMP degradation the "second messenger" to form for  NO, and  can activate soluble guanylate cyclise  to produce cGMP. This process counteracts the conversion of arginine to urea  and meanwhile can reactivate autophagy. Recent  studies  showed  that selective PDE5 inhibitors, raise hippocampal levels of GMPc improving memory in rats.

Audience Take Away:

1-this purely theoretical study clearly indicates that hypometabolism is the key point in the process of Alzheimer's formation
2- hypometabolism involves a modification of the functioning of the krebs cycle where arginine is preferably metabolized in urea
3-blockade of (Enos) simultaneously predisposes for arginine to preferentially activate motor with a decrease in autophagy
4- phosodiesterase inhibitors rebalance the conversion of arginine to NO by eNOS


Roberto Menicagli  is graduated, in Milan University  with postdoctoral studies in biochemistry and molecular genetics .Senior Researcher , in ENIRICERCHE,, the most important Italian Research Group, in the field of Chemistry and Biochemistry. Has been the chief and the responsible  of many projects for the Environment. and Public Health ,as Member of Scientific Committee ,of ENEA-CNR. Director of Roma Biomed Research Lab is specialist in  metabolomic study and for the  impact of environmental factors  on the human health ,publishing , 25 manuscripts  and an E- book. Is  the principal author of 4 international patent ,in the field of the environment, and biomarkers.