Modification of Glial Cell Activation through Dendritic Cell Vaccination: Promises for Treatment of Neurodegenerative Diseases

Accumulation of misfolded tau, amyloid β (Aβ), and alpha-synuclein (α-syn) proteins is the fundamental contributor to many neurodegenerative diseases, namely Parkinson’s (PD) and AD. Such protein aggregations trigger activation of immune mechanisms in neuronal and glial, mainly M1-type microglia cells, leading to release of pro-inflammatory mediators, and subsequent neuronal dysfunction and apoptosis. Despite the described neurotoxic features for glial cells, recruitment of peripheral leukocytes to the brain and their conversion to neuroprotective M2-type microglia can mitigate neurodegeneration by clearing extracellular protein accumulations or residues. Based on these observations, it was speculated that Dendritic cell (DC)-based vaccination, by making use of DCs as natural adjuvants, could be used for treatment of neurodegenerative disorders. DCs potentiated by disease-specific antigens can also enhance T helper 2 (Th2)-specific immune response and by production of specific antibodies contribute to clearance of intracellular aggregations, as well as enhancing regulatory T cell response. Thus, enhancement of immune response by DC vaccine therapy can potentially augment glial polarization into the neuroprotective phenotype, enhance antibody production, and at the same time balance neuronal cells’ repair, renewal, and protection. The characteristic feature of this method of treatment is to maintain the equilibrium in the immune response rather than targeting a single mediator in the disease and their application in other neurodegenerative diseases should be addressed. However, the safety of these methods should be investigated by clinical trials.