Cell Clearing Systems Bridging Neuro-Immunity and Synaptic Plasticity

• Published in: International journal of molecular sciences Vol. 20; no. 9; p. 2197
• Main Authors: Limanaqi, Fiona, Biagioni, Francesca, Busceti, Carla Letizia, Ryskalin, Larisa, Soldani, Paola, Frati, Alessandro, Fornai, Francesco
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04-05-2019; MDPI
• Subjects: Animals; Antigen processing; Antigens; Autoimmune diseases; Autophagy; Biomarkers; Cell cycle; Cell differentiation; Cellular stress response; Central nervous system; Crosstalk; Cytokines; Differentiation (biology); Disease Susceptibility; Dopamine; Energy Metabolism; glia; glutamate; Homeostasis; Humans; Immune system; Immune System - cytology; Immune System - immunology; Immune System - metabolism; Immunity; Immunological diseases; immunoproteasome; Inflammation; Inflammation Mediators - metabolism; Lymphocytes T; Major histocompatibility complex; mTOR; Nervous system; neuro-inflammation; Neurodegenerative Diseases - etiology; Neurodegenerative Diseases - metabolism; Neuroimmunomodulation; Neuronal Plasticity; Neurotransmission; Neurotransmitters; Peptides; Phagocytosis; proteasome; Proteasome Endopeptidase Complex - metabolism; Proteins; Review; Synaptic plasticity; Synaptic strength; Synaptic Transmission; T-cells; T-cells; neuro-inflammation; proteasome; immunoproteasome; autophagy; mTOR; dopamine; glia; glutamate
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20092197

In recent years, functional interconnections emerged between synaptic transmission, inflammatory/immune mediators, and central nervous system (CNS) (patho)-physiology. Such interconnections rose up to a level that involves synaptic plasticity, both concerning its molecular mechanisms and the clinical outcomes related to its behavioral abnormalities. Within this context, synaptic plasticity, apart from being modulated by classic CNS molecules, is strongly affected by the immune system, and vice versa. This is not surprising, given the common molecular pathways that operate at the cross-road between the CNS and immune system. When searching for a common pathway bridging neuro-immune and synaptic dysregulations, the two major cell-clearing cell clearing systems, namely the ubiquitin proteasome system (UPS) and autophagy, take center stage. In fact, just like is happening for the turnover of key proteins involved in neurotransmitter release, antigen processing within both peripheral and CNS-resident antigen presenting cells is carried out by UPS and autophagy. Recent evidence unravelling the functional cross-talk between the cell-clearing pathways challenged the traditional concept of autophagy and UPS as independent systems. In fact, autophagy and UPS are simultaneously affected in a variety of CNS disorders where synaptic and inflammatory/immune alterations concur. In this review, we discuss the role of autophagy and UPS in bridging synaptic plasticity with neuro-immunity, while posing a special emphasis on their interactions, which may be key to defining the role of immunity in synaptic plasticity in health and disease.