Neuroinflammation is one of the host defensive mechanisms through which the nervous system protects itself from pathogenic and or infectious insults. Moreover, neuroinflammation occurs as one of the most common pathological outcomes in various neurological disorders, makes it the promising target. The present review focuses on elaborating the recent advancement in understanding molecular mechanisms of neuroinflammation and its role in the etiopathogenesis of various neurological disorders, especially Alzheimer's disease (AD), Parkinson's disease (PD), and Epilepsy. Furthermore, the current status of anti-inflammatory agents in neurological diseases has been summarized in light of different preclinical and clinical studies. Finally, possible limitations and future directions for the effective use of anti-inflammatory agents in neurological disorders have been discussed.

Neuroinflammation in neurological disorders: pharmacotherapeutic targets from bench to bedside.

Alzheimer's disease (AD), considered the most common type of dementia, is characterized by a progressive loss of memory, visuospatial, language and complex cognitive abilities. In addition, patients often show comorbid depression and aggressiveness. Aging is the major factor contributing to AD; however, the initial cause that triggers the disease is yet unknown. Scientific evidence demonstrates that AD, especially the late onset of AD, is not the result of a single event, but rather it appears because of a combination of risk elements with the lack of protective ones. A major risk factor underlying the disease is neuroinflammation, which can be activated by different situations, including chronic pathogenic infections, prolonged stress and metabolic syndrome. Consequently, many therapeutic strategies against AD have been designed to reduce neuro-inflammation, with very promising results improving cognitive function in preclinical models of the disease. The literature is massive; thus, in this review we will revise the translational evidence of these early strategies focusing in anti-diabetic and anti-inflammatory molecules and discuss their therapeutic application in humans. Furthermore, we review the preclinical and clinical data of nutraceutical application against AD symptoms. Finally, we introduce new players underlying neuroinflammation in AD: the activity of the endocannabinoid system and the intestinal microbiota as neuroprotectors. This review highlights the importance of a broad multimodal approach to treat successfully the neuroinflammation underlying AD.

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Can We Treat Neuroinflammation in Alzheimer's Disease?

Abstract Microglia are specialized dynamic immune cells in the central nervous system (CNS) that plays a crucial role in brain homeostasis and in disease states. Persistent neuroinflammation is considered a hallmark of many neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson's disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and primary progressive multiple sclerosis (MS). Colony stimulating factor 1-receptor (CSF-1R) is predominantly expressed on microglia and its expression is significantly increased in neurodegenerative diseases. Cumulative findings have indicated that CSF-1R inhibitors can have beneficial effects in preclinical neurodegenerative disease models. Research using CSF-1R inhibitors has now been extended into non-human primates and humans. This review article summarizes the most recent advances using CSF-1R inhibitors in different neurodegenerative conditions including AD, PD, HD, ALS and MS. Potential challenges for translating these findings into clinical practice are presented. 

/pdf/inhibition-of-colony-stimulating-factor-1-receptor-csf-1r-as-1jij0874.pdf

Inhibition of colony stimulating factor-1 receptor (CSF-1R) as a potential therapeutic strategy for neurodegenerative diseases: opportunities and challenges

Recent evidence indicates that gut microbiota could interact with the central nervous system and affect brain function, including cognition and memory. In this study, we investigated whether Bifidobacterium bifidum BGN4 (B. bifidum BGN4) and Bifidobacterium longum BORI (B. longum BORI) alleviated the pathological features in a mouse model of Alzheimer’s disease (AD). Administration of B. bifidum BGN4 and B. longum BORI effectively suppressed amyloidosis and apoptotic processes and improved synaptic plasticity by ameliorating the neuroinflammatory response and BDNF expression. Moreover, behavioral tests indicated that B. bifidum BGN4 and B. longum BORI attenuated the cognitive and memory disability of AD mice. Taken together, the present study highlights the therapeutic potential of B. bifidum BGN4 and B. longum BORI for suppressing the pathological features of AD.

/pdf/administration-of-bifidobacterium-bifidum-bgn4-and-4ebpcxdyzr.pdf

Administration of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI Improves Cognitive and Memory Function in the Mouse Model of Alzheimer's Disease

Microglia are the resident immune cells of the central nervous system contributing substantially to health and disease. There is increasing evidence that inflammatory microglia may induce or accelerate brain aging, by interfering with physiological repair and remodeling processes. Many viral infections affect the brain and interfere with microglia functions, including human immune deficiency virus, flaviviruses, SARS-CoV-2, influenza, and human herpes viruses. Especially chronic viral infections causing low-grade neuroinflammation may contribute to brain aging. This review elucidates the potential role of various neurotropic viruses in microglia-driven neurocognitive deficiencies and possibly accelerated brain aging.

https://www.mdpi.com/2073-4409/10/7/1836/pdf

Verónica Espinosa-Fernández

Papers

Can We Treat Neuroinflammation in Alzheimer's Disease?

Early intervention with ABA prevents neuroinflammation and memory impairment in a triple transgenic mice model of Alzheimer´s disease.

Design, Synthesis and Evaluation of Fluorescent Analogues of Abscisic Acid

ABA Supplementation Rescues IRS2 and BDNF mRNA Expression in a Triple-Transgenic Mice Model of Alzheimer’s Disease