Effects of sildenafil (Viagra, Pfizer) on the inflammatory profile of Parkinson's Disease

• Grant number: 17/19799-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2018
• Effective date (End): May 06, 2022
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Catarina Raposo Dias Carneiro
• Grantee: Davi Felipe de Almeida
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 19/11448-9 - Induction of the Parkinson's Disease model by 6-ohda (6-hydroxydopamine) and behavioral analysis, BE.EP.IC

Abstract

Parkinson's disease (PD) is a progressive neurological disorder that leads to the loss of motor function. It is the second most common neurodegenerative disease in the elderly over 65, affecting between 1 and 2% of the world population. The disease remains without cure and the available treatments are mainly to the control of the symptoms. Pathologically, it is caused by the death of nigrostriatal dopaminergic neurons, and by the presence of intracytoplasmic Lewy body containing ±-synuclein and other proteins. Evidences show that persistent inflammatory response, lymphocyte infiltration and glial cell activation are common findings in patients and animal models of PD and play a crucial role in the degeneration of dopaminergic neurons. The relevant role of the cyclic guanosine monophosphate (cGMP) signaling in the control of the neuroinflammation has directed researchers to investigate the effect of phosphodiesterase (PDEs - enzymes that degrade cGMP) inhibitors in neurological diseases. These drugs (sildenafil has been the most representative and studied among them) induce accumulation of cyclic nucleotides and seems to be safe and effective in experimental models of Alzheimer's disease, multiple sclerosis, stroke, and others. However, studies on the therapeutic effects of sildenafil in the PD model are scarce and unclear and there are no reports about the effect of sildenafil on the inflammatory parameters during the disease. Thus, the present work aims to contribute to clearify the effects of the chronic treatment with sildenafil on PD, by a pre-clinical study using in vivo model of the disease. The inflammatory profile will be characterized, analysing the resident CNS inflammatory response mediated by microglia and astrocytes, as well as the systemic parameters of inflammation. Concomitantly, an assessment of the clinical condition of the animals will be made. This study is relevant and may direct future clinical studies with the aim of repositioning sildenafil as an effective drug to the treatmento of PD. (AU)