Neuro-Degenerative Disease
Conditions
Keywords
Alzheimer disease, Parkinson disease, P2X7 receptor
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.
Interventions
DRUGMemantine, Dopamine receptor-agonists
The study do not provide any experimental drugs. Patientes will receive treatment routinary used by Neurologist for these diseases.
Sponsors
University of Pisa
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
45 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* history of strokes or any neurological disease; * patients assuming neuroleptic drugs; * atypical symptoms at onset.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 NFkB activity | each patient will be assessed one year after diagnosis | NFkB activity is measured using RT-PCR |
| 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 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 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 |
Countries
Italy
Outcome results
None listed