P2X7 Receptor, Inflammation and Pathophysiology of Neurodegenerative Diseases
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Change from baseline in serum α-synuclein
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 45 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •history of strokes or any neurological disease;
- •patients assuming neuroleptic drugs;
- •atypical symptoms at onset.
研究组 & 干预措施
PD + AD
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.
干预措施: Memantine, Dopamine receptor-agonists (Drug)
结局指标
主要结局
Change from baseline in serum α-synuclein
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: each patient will be assessed one year after diagnosis
NFkB activity is measured using RT-PCR
次要结局
未报告次要终点
研究者
Anna Solini
Associate Professor
University of Pisa