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Please use this identifier to cite or link to this item: http://hdl.handle.net/10277/818

Authors: Kustrimovic, Natasa
Internal Tutor: COSENTINO, MARCO
Title: Peripheral immunity in Parkinson’s disease
Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population and it is characterized by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra, presence of α-synuclein rich intraneuronal inclusions (Lewy bodies), and microglial activation. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system. Nevertheless, numerous evidences testify undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. In addition, active participation of immune system has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Emerging evidence suggests that CD4+ T lymphocytes contribute to neuroinflammation in PD. Since the mainstay of PD treatment is DA-substitution therapy and DA is an established transmitter connecting nervous and immune systems, we have examined the changes in the pool of different subtypes of CD4+ T lymphocytes in patients and in healthy subjects, with specific regard to dopaminergic receptor (DR) expression. In addition, several in vitro experiments were performed in order to establish potential changes in function of CD4+ T cells. Obtained results regarding the complex phenotypic and functional profile of CD4+ T cell subsets in PD patients strengthen the evidence that peripheral adaptive immunity is involved in PD and represents a target for the preclinical and clinical assessment of novel immunomodulating therapeutics.
Keywords: Parkinson’s disease, adaptive peripheral immunity, CD4+ T cells, neuroinflammation, alpha-synuclein
Issue Date: 2018
Language: eng
Doctoral course: Medicina clinica e sperimentale e Medical Humanities
Academic cycle: 31
Publisher: Università degli Studi dell'Insubria
Other information: The study described in this thesis was conducted under supervision of professor Marco Cosentino in the Center for Research in Medical Pharmacology, University of Insubria and supported by a research grant from Fondazione CARIPLO to Marco Cosentino (Project 2011-0504: Dopaminergic modulation of CD4+ lymphocytes: relevance for neurodegeneration and neuroprotection in Parkinson's disease - The dopaminergic neuro-immune connection)
Citation: Kustrimovic, N.Peripheral immunity in Parkinson’s disease (Doctoral Thesis, Università degli Studi dell'Insubria, 2018).

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