Toll-Like Receptors in Neurodegeneration

Dear Colleagues,

Toll-like receptors (TLRs) belong to pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns released by stressed neuronal cells and injured tissues. To date, 13 murine TLRs and 10 human TLRs have been identified. They are expressed as transmembrane receptors or in intracellular endosomal compartments. Most cells in the central nervous system (CNS) express TLRs; microglia express the full repertoire of TLRs.

The activation of TLRs elicits the release of pro-inflammatory mediators such as cytokines by activated microglia, contributing to the brain blood barrier (BBB) permeabilization, exacerbation of the inflammatory response and death of adjacent neuronal cell. Chronic neuroinflammation has been documented in all progressive neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s disease, or Multiple Sclerosis.

Neuroinflammation is a defense mechanism against toxic insults or stimuli that can perturb the homeostasis in the CNS. Nowadays, there is great interest in the study of the inflammatory-related diseases for which there is no cure. Therefore, prevention and search of novel pharmacological targets and compounds are the main challenge of scientific research. Despite physical separation by BBB, interactions between the CNS and the immune system occur during pathologic processes. Cellular responses involve both the innate and adaptive immune system and can be beneficial or detrimental depends on duration and the circumstance.

Accumulated clinical/preclinical evidences have proven TLRs to be critical in the neuroinflammatory diseases and can be associated with alpha synuclein accumulation. Oddly, some evidence seems to suggest a protective effect of TLRs in the context of the neurodegenerative process, while many others report suggest a pro-inflammatory role of these receptors. The role of TLRs in the brain is currently a matter of great debate and controversy.

This Special Issue thus focuses on the understanding of the underlying molecular mechanisms of neurodegenerative disorders pointing to TLRs signaling and protein accumulation. Modulation of TLRs signaling pathways could represent a new therapeutic approach for treating neurodegenerative diseases and could have a huge clinical value.

Dr. Carmela Conte
Prof. Dr. Tomasso Beccari
Guest Editors

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• Toll Like Receptors
• DAMPs
• alpha synuclein
• cytokines
• neuroinflammation
• age-related diseases
• Parkinson’s disease
• neurodegenerative disease
• autophagy
• natural products