P2X7 Receptor, Inflammation and Neurodegenerative Diseases
- Conditions
- Neuro-Degenerative Disease
- Interventions
- Registration Number
- NCT03918616
- Lead Sponsor
- University of Pisa
- Brief Summary
Parkinson disease (PD) is a chronic degenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Its pathophysiological mechanisms are still partially unknown; a main role seems to be played by chronic neuroinflammation. A few reports have addressed the possible involvement of the inflammasome in PD, just describing the protective effect of P2X7 purinergic receptor (P2X7R) blockers in murine models of the disease and in microglial cells, where NLRP3 is activated by α-Synuclein, triggering a neuroinflammation that contributes to degeneration of dopaminergic neurons. It is still unclear whether, in addition to the increased brain expression and function of the nucleotide-binding domain, leucine-rich repeat, pyrin domain containing type 3 (NLRP3) inflammasome platform, a systemic activation of such complex might participate in the pathogenesis of PD, which could be the role of the P2X7R in this scenario, and whether such patterns undergo any specific epigenetic regulation. The present study has been designed to address these issues.
- Detailed Description
The day of the study patientes underwent a complete clinical evaluation and assessment of psycho-physical abilities using specific test such as Mini-Mental State Examination (MMSE), Cognitive Alzheimer's Disease Assessment Scale (ADAS-Cog), Clinical Dementia Rating Scale, Unified Parkinson's Disease Rating Scale (UPDRS). Blood samples were collected from an antecubital vein to assess serum and plasma aliquots for blood routine analysis and RNA and protein extraction from circulating lymphomonocytes.
To explore a putative epigenetic regulation of such complex scenario some circulating miRNAs likely involved in the pathogenesis of neurological diseases and neuro-inflammation will be measured.
Expression and functional activity of P2X7R-inflammasome complex will be measured by PCR and WB. Acute phase cytokines inflammasome-related levels will be determined by ELISA. Biochemical parameters (fasting glucose, lipid profile, serum creatinine, uric acid) will be measured by standard methods in the biochemistry laboratory of the University Hospital in Pisa. The same determinations will be repeated after one year from the first visit.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
- newly-diagnosed PD or AD;
- no previous specific treatment;
- no systemic inflammatory or immunological disease and/or cancer;
- no anti-inflammatory drugs assumed in the three months preceding the enrolment;
- patients able to consent.
- history of strokes or any neurological disease;
- patients assuming neuroleptic drugs;
- atypical symptoms at onset.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description PD + AD Memantine, Dopamine receptor-agonists Patients with newly-diagnosed (onset of suggestive symptoms not later than 3 months) Parkinson disease (PD) or Alzheimer disease (AD) with no previous specific treatment, no anti-inflammatory drugs assumed in the three months preceding the enrolment and no chronic inflammatory diseases or cancer.
- Primary Outcome Measures
Name Time Method Change from baseline in serum α-synuclein each patient will be assessed one year after diagnosis Circulating levels of α-synuclein are determined using high sensitivity Quantikine enzyme-linked immunosorbent assay (ELISA) and express as \[ng/ml\]
Change from baseline in circulating levels of microRNA miR-30 and miR-7 each patient will be assessed one year after diagnosis Circulating levels of microRNA miR-30 and miR-7 are measured using TaqMan Advanced MicroRNA Assays
Change from baseline in P2X7R-inflammasome activity each patient will be assessed one year after diagnosis NLRP3-ASC-Caspase-1 activity is measured using RT-PCR
Change from baseline in serum IL-1β each patient will be assessed one year after diagnosis Circulating levels of IL-1β are determined using high sensitivity Quantikine enzyme-linked immunosorbent assay (ELISA) and express as \[pg/ml\]
Change from baseline in serum IL-18 each patient will be assessed one year after diagnosis Circulating levels of IL-18 are determined using high sensitivity Quantikine enzyme-linked immunosorbent assay (ELISA) and express as \[pg/ml\]
Change from baseline in NFkB activity each patient will be assessed one year after diagnosis NFkB activity is measured using RT-PCR
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
University of Pisa
🇮🇹Pisa, Italy