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Digital archive of theses discussed at the University of Pisa

 

Thesis etd-01172022-163807


Thesis type
Tesi di specializzazione (4 anni)
Author
PELLEGRINI, CAROLINA
URN
etd-01172022-163807
Thesis title
Gut-brain axis in neurological diseases: pathophysiological and pharmacological implications
Department
MEDICINA CLINICA E SPERIMENTALE
Course of study
FARMACOLOGIA E TOSSICOLOGIA CLINICA (non medici)
Supervisors
relatore Prof. Fornai, Matteo
Keywords
  • Parkinson's disease
  • Alzheimer's disease
  • bowel inflammation
  • NLRP3 inflammasome
  • animal models
  • patients
  • alpha synuclien
  • gut microbiota
  • amyloid beta
Graduation session start date
21/02/2022
Availability
Withheld
Release date
21/02/2062
Summary
Growing evidence suggest that, in brain diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), changes in gut microbiota and enteric neuro-immune system alterations could contribute to intestinal dysfunctions as well as the initiation and upward spreading of the disease, via gut-brain axis. Of note, the NLRP3 inflammasome multiprotein complex has been found to act as a key player in the shaping the peripheral and central immune/inflammatory responses in brain diseases. The present research project has been undertaken to investigate the role of gut-brain axis in neurological diseases, including PD and AD, by means of investigations in a transgenic model of PD (A53T mouse), AD model of accelerated senescence (SAMP8 mouse) and PD patients. The results of the present research project suggest that impairments of intestinal epithelial barrier, neurogenic immune/inflammatory responses, characterized by activation of NLRP3 inflammasome signalling, AD and PD-related protein deposition and bowel dysmotility represent early events in PD and AD and could contribute to central pathology via gut-brain axis. In this setting, a novel gut-directed locally acting NLRP3 inhibitor counteracted cognitive impairment, central and peripheral inflammation and barrier impairments in AD mice. Human experiments have shown that PD patients were characterized by: 1) enteric inflammation and 2) intestinal mucosal barrier impairments that could contribute functional bowel abnormalities as well as central pathology. In conclusion, intestinal symptoms represent early events in AD and PD and the inhibition of gut inflammation could represent an useful therapeutical approach to alleviate intestinal symptoms and to counteract disease progression.
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