P2X7 Receptor, Inflammation and Neurodegenerative Diseases
Condition: Neuro-Degenerative Disease
MeSH terms: Neurodegenerative Diseases; Inflammation
Study type: Observational

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.
    

Intervention name(s): Memantine, Dopamine receptor-agonists
Intervention type(s): Drug
Intervention description(s): The study do not provide any experimental drugs. Patientes will receive treatment routinary used by Neurologist for these diseases.
Other intervention name(s): Memantine: Ebixa. Dopamine receptor-agonists: Sinemet, Sirio.
Intervention MeSH terms: Dopamine; Memantine; Dopamine Agonists
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The study consecutively enrolled 50 newly-diagnosed, treatment-naive PD or AD individuals
        among those referring to the Neurology Unit, University Hospital in Pisa, Italy.
      
Biospecimen description: 
      Serum samples
    
Keywords: Alzheimer disease; Parkinson disease; P2X7 receptor