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Curr Med Chem. 2018 Oct 9. doi: 10.2174/0929867325666181009161048. [Epub ahead of print]

Peripheral Immunity, Immunoaging and Neuroinflammation in Parkinson's Disease.

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1
Center of Research in Medical Pharmacology, University of Insubria, Varese. Italy.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder among elderly population, and it is depicted by the degeneration of dopaminergic neurons in the midbrain which is progressive. Up to the present time, the precise cause remains ill-defined and the mechanism of neurons death indeterminate. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidences have been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. Nevertheless, active participation of immune system as well has been noted, such as, elevated levels of cytokines in peripheral blood, as well as, the presence of auto antibodies. In addition, the infiltration of T cell in CNS has been reported. Moreover, infiltration and reactivation of those T cells could exacerbate neuroinflammation to greater neurotoxic levels. Hence, peripheral inflammation is able to prime microglia into pro-inflammatory phenotype, which can trigger stronger response in CNS further perpetuating the on-going neurodegenerative process. In the present review, the interplay between neuroinflammation and the peripheral immune response in the pathobiology of PD will be discussed. First of all, an overview of regulation of microglial activation and neuroinflammation is summarized and discussed. Afterwards, we try to collectively analyze changes that occurs in peripheral immune system of PD patients and trying to link them to the potential exacerbation of the neuroinflammation and hence the symptoms of the disease. In the end, we summarize some of proposed immunotherapies for treatment of PD.

KEYWORDS:

Parkinson’s disease; alpha-synuclein; immunoaging; immunomodulation. ; neuroinflammation; peripheral immunity

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