Neurodegenerative diseases: The immunological perspective

Abstract

Increasing evidence supports the notion that the neurodegenerative process occurring in Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis (ALS) does not only imply the neuronal compartment but also involves a strong interaction with the immunological cells of the Central Nervous System (CNS), primarily microglia. Starting from the observation that the neurodegenerative disorders are frequent in elderly individuals, who have an immunological background that possibly favors this process, it is evident that a dysregulation of innate immune response triggered by misfolded and aggregated proteins, or by endogenous molecules released by injured neurons, directly contributes to disease pathogenesis and progression. There are important differences in the immunological processes occurring in AD, PD, ALS involving microglial function. Furthermore, although the contribution of adaptive immune cells in AD seems to be modest, in PD and especially in ALS models, T cells can influence microglial phenotype, inducing neuroprotection. A better understanding of the immunological mechanisms involved in the different phases of the neurodegenerative processes observed in AD, PD, ALS could effectively contribute to the development of new preventive and therapeutic strategies for such diseases.

Keywords: Alzheimer's disease; Amyotrophic lateral sclerosis; Innate immunity; Microglia; Neuroinflammation; Parkinson's disease.