Neuroinflammation as a therapeutic target in neurodegenerative diseases

Gordon, Richard D.; Woodruff, Trent M.

doi:10.1016/b978-0-12-805120-7.00003-8

Cited by 12 publications

(8 citation statements)

References 226 publications

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“…Evidences suggest that controlled neuroinflammation is crucial for tissue repair within the brain [62, 63]. However, prolonged exposure to inflammatory conditions in the brain has been linked with the development of neurodegenerative diseases, such as the Alzheimer's and Parkinson's diseases, and multiple sclerosis [64]. In Alzheimer's disease, misfolded and aggregated proteins are recognized by microglia and activate an innate immune response characterized by the release of inflammatory mediators, contributing to the disease progression and severity [65].…”

Section: The Role Of the Endocannabinoid System In Neuroinflammationmentioning

confidence: 99%

Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer

Pellati

Borgonetti

Brighenti

et al. 2018

BioMed Research International

298

242

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In the last decades, a lot of attention has been paid to the compounds present in medicinal Cannabis sativa L., such as Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and their effects on inflammation and cancer-related pain. The National Cancer Institute (NCI) currently recognizes medicinal C. sativa as an effective treatment for providing relief in a number of symptoms associated with cancer, including pain, loss of appetite, nausea and vomiting, and anxiety. Several studies have described CBD as a multitarget molecule, acting as an adaptogen, and as a modulator, in different ways, depending on the type and location of disequilibrium both in the brain and in the body, mainly interacting with specific receptor proteins CB1 and CB2. CBD is present in both medicinal and fibre-type C. sativa plants, but, unlike Δ9-THC, it is completely nonpsychoactive. Fibre-type C. sativa (hemp) differs from medicinal C. sativa, since it contains only few levels of Δ9-THC and high levels of CBD and related nonpsychoactive compounds. In recent years, a number of preclinical researches have been focused on the role of CBD as an anticancer molecule, suggesting CBD (and CBD-like molecules present in the hemp extract) as a possible candidate for future clinical trials. CBD has been found to possess antioxidant activity in many studies, thus suggesting a possible role in the prevention of both neurodegenerative and cardiovascular diseases. In animal models, CBD has been shown to inhibit the progression of several cancer types. Moreover, it has been found that coadministration of CBD and Δ9-THC, followed by radiation therapy, causes an increase of autophagy and apoptosis in cancer cells. In addition, CBD is able to inhibit cell proliferation and to increase apoptosis in different types of cancer models. These activities seem to involve also alternative pathways, such as the interactions with TRPV and GRP55 receptor complexes. Moreover, the finding that the acidic precursor of CBD (cannabidiolic acid, CBDA) is able to inhibit the migration of breast cancer cells and to downregulate the proto-oncogene c-fos and the cyclooxygenase-2 (COX-2) highlights the possibility that CBDA might act on a common pathway of inflammation and cancer mechanisms, which might be responsible for its anticancer activity. In the light of all these findings, in this review we explore the effects and the molecular mechanisms of CBD on inflammation and cancer processes, highlighting also the role of minor cannabinoids and noncannabinoids constituents of Δ9-THC deprived hemp.

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Section: The Role Of the Endocannabinoid System In Neuroinflammationmentioning

confidence: 99%

Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer

Pellati

Borgonetti

Brighenti

et al. 2018

BioMed Research International

298

242

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“…PRRs, such as RAGE, Mac1, and TLRs, constitute potential targets for treatment, given the view that DAMPs and misfolded proteins mediate neuroinflammation by interacting with multiple PRRs. Moreover, stimulating PRRs with neuronal DAMPs was found to be associated with the activation of downstream pro-inflammatory pathways, such as NOX2, iNOS, and TNFα ( 1 ). Thus, efficient targeting of PRRs involved in each neurodegenerative disease could be a possible strategy to decrease reactive gliosis and chronic self-perpetuating neuroinflammation and neurotoxicity.…”

Section: Results: Therapeutic Strategies Targeting Neuroinflammation In the Management Of Neurodegenerative Diseasesmentioning

confidence: 99%

“…Neuroinflammation, which is an important process for maintaining healthy central nervous system (CNS) function following injuries such as physical trauma and infections, is highly regulated due to the lack of regenerative ability of post-mitotic cells of the nervous system. It also constitutes a major component of many neurodegenerative ( 1 ) and psychiatric disorders ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

Immunotherapies for Neurodegenerative Diseases

et al. 2021

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The current treatments for neurodegenerative diseases are mostly symptomatic without affecting the underlying cause of disease. Emerging evidence supports a potential role for immunotherapy in the management of disease progression. Numerous reports raise the exciting prospect that either the immune system or its derivative components could be harnessed to fight the misfolded and aggregated proteins that accumulate in several neurodegenerative diseases. Passive and active vaccinations using monoclonal antibodies and specific antigens that induce adaptive immune responses are currently under evaluation for their potential use in the development of immunotherapies. In this review, we aim to shed light on prominent immunotherapeutic strategies being developed to fight neuroinflammation-induced neurodegeneration, with a focus on innovative immunotherapies such as vaccination therapy.

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“…Anomalous microglia activity has been detected in neurodegenerative diseases [16]. Growing evidence has proven that alleviating neuroinflammation is a valid strategy in the treatment course of neurodegenerative diseases [17][18][19]. Interestingly, MAO-B inhibitors were reported to repress microglia-contributed neuroinflammation [20,21].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of O6-Aminoalkyl-Hispidol Analogs as Multifunctional Monoamine Oxidase-B Inhibitors towards Management of Neurodegenerative Diseases

et al. 2023

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Oxidative catabolism of monoamine neurotransmitters by monoamine oxidases (MAOs) produces reactive oxygen species (ROS), which contributes to neuronal cells’ death and also lowers monoamine neurotransmitter levels. In addition, acetylcholinesterase activity and neuroinflammation are involved in neurodegenerative diseases. Herein, we aim to achieve a multifunctional agent that inhibits the oxidative catabolism of monoamine neurotransmitters and, hence, the detrimental production of ROS while enhancing neurotransmitter levels. Such a multifunctional agent might also inhibit acetylcholinesterase and neuroinflammation. To meet this end goal, a series of aminoalkyl derivatives of analogs of the natural product hispidol were designed, synthesized, and evaluated against both monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B). Promising MAO inhibitors were further checked for the inhibition of acetylcholinesterase and neuroinflammation. Among them, compounds 3aa and 3bc were identified as potential multifunctional molecules eliciting submicromolar selective MAO-B inhibition, low-micromolar AChE inhibition, and the inhibition of microglial PGE2 production. An evaluation of their effects on memory and cognitive impairments using a passive avoidance test confirmed the in vivo activity of compound 3bc, which showed comparable activity to donepezil. In silico molecular docking provided insights into the MAO and acetylcholinesterase inhibitory activities of compounds 3aa and 3bc. These findings suggest compound 3bc as a potential lead for the further development of agents against neurodegenerative diseases.

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Neuroinflammation as a therapeutic target in neurodegenerative diseases

Cited by 12 publications

References 226 publications

Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer

Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer

Immunotherapies for Neurodegenerative Diseases

Synthesis and Biological Evaluation of O6-Aminoalkyl-Hispidol Analogs as Multifunctional Monoamine Oxidase-B Inhibitors towards Management of Neurodegenerative Diseases

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