Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

Abstract

The increasing life expectancy has led to a higher incidence of age-related neurodegenerative conditions. Within this framework, neuroinflammation emerges as a significant contributing factor. It involves the activation of microglia and astrocytes, leading to the release of pro-inflammatory cytokines and chemokines and the infiltration of peripheral leukocytes into the central nervous system (CNS). These instances result in neuronal damage and neurodegeneration through activated nucleotide-binding domain and leucine-rich repeat containing (NLR) family pyrin domain containing protein 3 (NLRP3) and nuclear factor kappa B (NF-kB) pathways and decreased nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Due to limited effectiveness regarding the inhibition of neuroinflammatory targets using conventional drugs, there is challenging growth in the search for innovative therapies for alleviating neuroinflammation in CNS diseases or even before their onset. Our results indicate that interventions focusing on Interleukin-Driven Immunomodulation, Chemokine (CXC) Receptor Signaling and Expression, Cold Exposure, and Fibrin-Targeted strategies significantly promise to mitigate neuroinflammatory processes. These approaches demonstrate potential anti-neuroinflammatory effects, addressing conditions such as Multiple Sclerosis, Experimental autoimmune encephalomyelitis, Parkinson’s Disease, and Alzheimer’s Disease. While the findings are promising, immunomodulatory therapies often face limitations due to Immune-Related Adverse Events. Therefore, the conduction of randomized clinical trials in this matter is mandatory, and will pave the way for a promising future in the development of new medicines with specific therapeutic targets.

A Decade of Dedication: Pioneering Perspectives on Neurological Diseases and Mental Illnesses

“…Neuroinflammation is increasingly recognized as a significant factor in a variety of brain diseases, with microglia and monocytes playing an important role in the robust activation of the NOD-, LRR-and pyrin domain-containing protein 3 (NLRP3) inflammasome [128][129][130]. Chiarini et al discuss the regulation of NLRP3 and its involvement in diverse neurological disorders [81].…”

The Vital Role of Melatonin and Its Metabolites in the Neuroprotection and Retardation of Brain Aging

“…Furthermore, melatonin is able to inhibit NLRP3 activation and to reduce pro-inflammatory factors, via promoting the activation of Nrf2/ARE signaling [104]. The NLRP3 inflammasome is a protein complex that initiates an inflammatory form of cell death and triggers the release of IL-1β and IL-18 and has also been implicated in neurodegenerative diseases [105,106]. Therefore, the suppression of the NLRP3 inflammasome by melatonin controls neuroinflammation and attenuates mitochondrial dysfunction.…”

Innovation at the Intersection: Emerging Translational Research in Neurology and Psychiatry

“…Neurotransmitters can modulate the neural activity and synaptic plasticity, which are essential for learning, memory, and cognition [160,162,181,182]. Neurotransmitters can also confer neuroprotection, which is the ability of the nervous system to resist or recover from damage caused by various insults, such as oxidative stress, excitotoxicity, inflammation, and degeneration [183][184][185][186][187]. One of the most important neurotransmitters in the nervous system is glutamate, which is the main excitatory neurotransmitter that mediates rapid synaptic transmission and long-term potentiation [188].…”