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The role of innate and adaptive immunity in Parkinson's disease.

ABSTRACT: In recent years, inflammation has become implicated as a major pathogenic factor in the onset and progression of Parkinson's disease. Understanding the precise role for inflammation in PD will likely lead to understanding of how sporadic disease arises. In vivo evidence for inflammation in PD includes microglial activation, increased expression of inflammatory genes in the periphery and in the central nervous system (CNS), infiltration of peripheral immune cells into the CNS, and altered composition and phenotype of peripheral immune cells. These findings are recapitulated in various animal models of PD and are reviewed herein. Furthermore, we examine the potential relevance of PD-linked genetic mutations to altered immune function and the extent to which environmental exposures that recapitulate these phenotypes, which may lead to sporadic PD through similar mechanisms. Given the implications of immune system involvement on disease progression, we conclude by reviewing the evidence supporting the potential efficacy of immunomodulatory therapies in PD prevention or treatment. There is a clear need for additional research to clarify the role of immunity and inflammation in this chronic, neurodegenerative disease.

SUBMITTER: Kannarkat GT

PROVIDER: S-EPMC4102262 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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The role of innate and adaptive immunity in Parkinson's disease.

Kannarkat George T GT Boss Jeremy M JM Tansey Malú G MG

Journal of Parkinson's disease 20130101 4

In recent years, inflammation has become implicated as a major pathogenic factor in the onset and progression of Parkinson's disease. Understanding the precise role for inflammation in PD will likely lead to understanding of how sporadic disease arises. In vivo evidence for inflammation in PD includes microglial activation, increased expression of inflammatory genes in the periphery and in the central nervous system (CNS), infiltration of peripheral immune cells into the CNS, and altered composi ...[more]

PMID: 24275605

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Project description:Inflammatory mechanisms have been increasingly implicated in the origin of seizures and epilepsy. These mechanisms are involved in the genesis of encephalitides in which seizures are a common complaint. Experimental and clinical evidence suggests different inflammatory responses in the brains of patients with epilepsy depending on the etiology. In general, activation of both innate and adaptive immunity plays a role in refractory forms of epilepsy. Epilepsies in which seizures develop after infiltration of cells of the adaptive immune system in the central nervous system (CNS) include a broad range of epileptic disorders with different (known or unknown) etiologies. Infiltration of lymphocytes is observed in autoimmune epilepsies, especially the classical paraneoplastic encephalitides with antibodies against intracellular tumor antigens. The presence of lymphocytes in the CNS also has been found in focal cerebral dysplasia type 2 and in cortical tubers. Various autoantibodies have been shown to be associated with temporal lobe epilepsy (TLE) and hippocampal sclerosis of unknown etiology, which may be due to the presence of viral DNA. During the last decade, an increasing number of antineuronal autoantibodies directed against membranous epitopes have been discovered and are associated with various neurologic syndromes, including limbic encephalitis. A major challenge in epilepsy is to define biomarkers, which would allow the recognition of patient populations who might benefit from immune-modulatory therapies. Some peripheral inflammatory markers appear to be differentially expressed in patients with medically controlled and medically refractory and, as such, could be used for diagnostic, prognostic, or therapeutic purposes. Establishing an autoimmune basis in patients with drug-resistant epilepsy allows for efficacious and targeted immunotherapy. Although current immunotherapies can give great benefit to the correctly identified patient, there are limitations to their efficacy and they may have considerable side effects. Thus the identification of new immunomodulatory compounds remains of utmost importance.

Dataset Information

The role of innate and adaptive immunity in Parkinson's disease.

Publications

The role of innate and adaptive immunity in Parkinson's disease.

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