Title:Peripheral Immunity, Immunoaging and Neuroinflammation in Parkinson’s Disease
Volume: 26
Issue: 20
Author(s): Natasa Kustrimovic, Franca Marino and Marco Cosentino*
Affiliation:
- Center of Research in Medical Pharmacology, University of Insubria, Varese,Italy
Keywords:
Parkinson's disease, neuroinflammation, peripheral immunity, alpha-synuclein, immunoaging, immunomodulation.
Abstract:
Parkinson’s disease (PD) is the second most common neurodegenerative disorder
among elderly population, characterized by the progressive degeneration of dopaminergic
neurons in the midbrain. To date, exact cause remains unknown and the mechanism of neurons
death uncertain. It is typically considered as a disease of central nervous system (CNS).
Nevertheless, numerous evidence has been accumulated in several past years testifying 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. Nevertheless, active participation of immune system as well 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. 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, suggesting
that these peripheral immune challenges can exacerbate the process of neuroinflammation
and hence the symptoms of the disease. In the end, we summarize some of proposed
immunotherapies for treatment of PD.
