Targets and Mechanisms in Prevention of Parkinson's Disease through Immunomodulatory Treatments

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world; however, there is no cure for it. Current treatments only relieve some of the symptoms, without ceasing the disease, and lose efficacy with prolonged treatment. Considerable evidence shows that persistent inflammatory responses, involving T cell infiltration and glial cell activation, are common characteristics of human patients and play a crucial role in the degeneration of dopaminergic neurons. Therefore, it is important to develop therapeutic strategies that can impede or halt the disease through the modulation of the peripheral immune system by aiming at controlling the existing neuroinflammation. Most of the immunomodulatory therapies designed for the treatment of Parkinson 0 s disease are based on vaccines using AS or antibodies against it; yet, it is of significant interest to explore other formulations that could be used as therapeutic agents. Several vaccination procedures have shown that inducing regulatory T cells in the periphery is protective in PD animal models. In this regard, the formulation glatiramer acetate (Copaxone â ), extensively used for the treatment of multiple sclerosis, could be a suitable candidate due to its capability to increase the number and suppressor capacity of regulatory T cells. In this review, we will present some of the recent immunomodulatory therapies for PD including vaccinations with AS or glatiramoids, or both, as treatments of PD pathology.

Parkinson’s disease patients have a complex phenotypic and functional Th1 bias: cross-sectional studies of CD4+ Th1/Th2/T17 and Treg in drug-naïve and drug-treated patients

“…Peripheral adaptive immunity in PD has been the subject of increasing interest over the last two decades, since in animal models of neurodegeneration T lymphocytes provide a major contribution to neuroinflammation and neuronal death, and targeting the peripheral immune system, e.g., by increasing Treg activity, may result in effective neuroprotection [ 32 , 33 ]. Various studies indeed suggest the occurrence of peripheral immune changes in PD patients, including decreased CD4+/CD8+ T-cell ratios, fewer CD4 + CD25+ T cells, increased ratios of IFN-γ-producing to IL-4-producing T cells [ 34 ], and decreased CD4+ T lymphocytes and CD19+ B cells [ 35 , 36 ].…”

microRNAs in Parkinson’s Disease: From Pathogenesis to Novel Diagnostic and Therapeutic Approaches

“…Indeed, the causes and mechanisms contributing to DAergic degeneration are ill-defined [ 11 ] and, currently, there is no cure for PD but only treatments able to relieve the symptoms and to improve the quality of life. These treatments include: supportive therapies (such as rehabilitation, through the use of physiotherapy, occupational therapy and speech and language therapy) and palliative medications (e.g., the DA precursor levodopa (L-DOPA), dopamine agonists, catechol-O-methyl transferase (COMT) inhibitors, monoamine oxidase B (MAO-B) inhibitors, amantadine and anti-cholinergic molecules and immunomodulatory therapies) [ 13 , 14 , 15 , 16 ]. If the palliative drugs fail to adequately control patients’ symptoms, deep brain stimulation (DBS) can be used.…”

Neuroinflammation is associated with infiltration of T cells in Lewy body disease and ɑ-synuclein transgenic models.

“…Another study identified increased numbers of Th1 and Th17 cells with a concomitant decrease in Th2 and Treg cells in PD patients and animals models [66]. In addition to the potentially neurotoxic effects of cytokines produced by Th1/Th17 cells [67,68], Th2 and Treg cells are thought to regulate innate immunity in the CNS, suggesting that the imbalance in T cell types may contribute to overactive glia and chronic inflammation [69][70][71]. A recent study in MSA patients showed increased infiltration in the brain by CD4 + and CD8 + T cells.…”