1,721,132 research outputs found
Cannabinoids and Neurogenesis: The Promised Solution for Neurodegeneration?
No full textThe concept of neurons as irreplaceable cells does not hold true today. Experiments and evidence of neurogenesis, also, in the adult brain give hope that some compounds or drugs can enhance this process, helping to reverse the outcomes of diseases or traumas that once were thought to be everlasting. Cannabinoids, both from natural and artificial origins, already proved to have several beneficial effects (e.g., anti-inflammatory, anti-oxidants and analgesic action), but also capacity to increase neuronal population, by replacing the cells that were lost and/or regenerate a damaged nerve cell. Neurogenesis is a process which is not highly represented in literature as neuroprotection, though it is as important as prevention of nervous system damage, because it can represent a possible solution when neuronal death is already present, such as in neurodegenerative diseases. The aim of this review is to resume the experimental evidence of phyto- and synthetic cannabinoids effects on neurogenesis, both in vitro and in vivo, in order to elucidate if they possess also neurogenetic and neurorepairing properties
Nrf2 Activation: Involvement in Central Nervous System Traumatic Injuries. A Promising Therapeutic Target of Natural Compounds
No full textCentral nervous system (CNS) trauma, such as traumatic brain injury (TBI) and spinal cord injury (SCI), represents an increasingly important health burden in view of the preventability of most injuries and the complex and expensive medical care that they necessitate. These injuries are characterized by different signs of neurodegeneration, such as oxidative stress, mitochondrial dysfunction, and neuronal apoptosis. Cumulative evidence suggests that the transcriptional factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial defensive role in regulating the antioxidant response. It has been demonstrated that several natural compounds are able to activate Nrf2, mediating its antioxidant response. Some of these compounds have been tested in experimental models of SCI and TBI, showing different neuroprotective properties. In this review, an overview of the preclinical studies that highlight the positive effects of natural bioactive compounds in SCI and TBI experimental models through the activation of the Nrf2 pathway has been provided. Interestingly, several natural compounds can activate Nrf2 through multiple pathways, inducing a strong antioxidant response against CNS trauma. Therefore, some of these compounds could represent promising therapeutic strategies for these pathological conditions
The Role of Cannabinoid Type 2 Receptors in Parkinson’s Disease
No full textParkinson’s disease (PD) is the second most frequent neurodegenerative disease and currently represents a clear unmet medical need. Therefore, novel preventive and therapeutic strategies are needed. Cannabinoid type 2 (CB2) receptors, one of the components of the endocannabinoid system, can regulate neuroinflammation in PD. Here, we review the current preclinical and clinical studies investigating the CB2 receptors in PD with the aim to clarify if these receptors could have a role in PD. Preclinical data show that CB2 receptors could have a neuroprotective action in PD and that the therapeutic targeting of CB2 receptors could be promising. Indeed, it has been shown that different CB2 receptor-selective agonists exert protective effects in different PD models. Moreover, the alterations in the expression of CB2 receptors observed in brain tissues from PD animal models and PD patients suggest the potential value of CB2 receptors as possible novel biomarkers for PD. However, to date, there is no direct evidence of the role of CB2 receptors in PD. Further studies are strongly needed in order to fully clarify the role of CB2 receptors in PD and thus pave the way to novel possible diagnostic and therapeutic opportunities for PD
Target regulation of PI3K/Akt/mTOR pathway by cannabidiol in treatment of experimental multiple sclerosis
No full textCannabidiol exerts protective effects in an in vitro model of Parkinson's disease activating AKT/mTOR pathway
No full text: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of the nigrostriatal dopaminergic pathway with loss of substantia nigra pars compacta neurons and dopamine depletion. Various natural compounds showed protective actions against PD. In this work, the protective effects of cannabidiol (CBD), obtained from Cannabis sativa, were evaluated in retinoic acid differentiated SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP+), an in vitro PD model. In order to evaluate which receptor is involved in CBD actions CB1, CB2 and TRPV1 receptor antagonists were used. CBD counteracted the loss of cell viability caused by MPP+, reducing apoptosis as demonstrated by the reduction of Bax and caspase 3. Moreover, CBD reduced the nuclear levels of PARP-1. The protective effects of CBD seem to be mediated by the activation of ERK and AKT/mTOR pathways. The treatment with AKT1/2 inhibitor and the mTOR inhibitor rapamycin abolished CBD protective effects. The CBD-induced ERK activation may be mediated by CBD interaction with CB2 and TRPV1. We also investigated the protein levels of the autophagic proteins LC3 and beclin 1. CBD reduced the MPP+-induced increase of LC3 by CB2 and TRPV1 receptors. These data suggested the involvement of ERK in the modulation of autophagy. However, beclin 1 levels were not modified neither by MPP+ nor by CBD. These results indicated that CBD may exert preventive and protective actions in PD
Serum-Free Cultures: Could They Be a Future Direction to Improve Neuronal Differentiation of Mesenchymal Stromal Cells?
No full textMesenchymal stem/stromal cells (MSCs) are undifferentiated cells with multilinear potential, known for their immunomodulatory and regenerative properties. Although the scientific community is working to improve their application, concerns limit their use to repair tissues following neurological damage. One of these obstacles is represented by the use of culture media supplemented with fetal bovine serum (FBS), which, due to its xenogenic nature and the risk of contamination, has increased scientific, ethical and safety problems. Therefore, the use of serum-free media could improve MSC culture methods, avoiding infectious and immunogenic transmission problems as well as MSC bioprocesses, without the use of animal components. The purpose of our review is to provide an overview of experimental studies that demonstrate that serum-free cultures, along with the supplementation of growth factors or chemicals, can lead to a more defined and controlled environment, enhancing the proliferation and neuronal differentiation of MSCs
Regenerative Effects of Exosomes-Derived MSCs: An Overview on Spinal Cord Injury Experimental Studies
No full textSpinal cord injury (SCI) is a devastating condition usually induced by the initial mechanical insult that can lead to permanent motor and sensory deficits. At present, researchers are investigating potential therapeutic strategies to ameliorate the neuro-inflammatory cascade that occurs post-injury. Although the use of mesenchymal stromal/stem (MSCs) as a potential therapy in application to regenerative medicine promoted anti-inflammatory and neuroprotective effects, several disadvantages limit their use. Therefore, recent studies have reported the effects of exosomes-derived MSCs (MSC-EXOs) as an innovative therapeutic option for SCI patients. It is noteworthy that MSC-EXOs can maintain the integrity of the blood-spinal cord barrier (BSCB), promoting angiogenic, proliferative, and anti-oxidant effects, as well as immunomodulatory, anti-inflammatory, and antiapoptotic properties. Therefore, in this study, we summarized the preclinical studies reported in the literature that have shown the effects of MSC-EXOs as a new molecular target to counteract the devastating effects of SCI
Efficacy of Sulforaphane in Neurodegenerative Diseases
No full textSulforaphane (SFN) is a phytocompound belonging to the isothiocyanate family. Although it was also found in seeds and mature plants, SFN is mainly present in sprouts of many cruciferous vegetables, including cabbage, broccoli, cauliflower, and Brussels sprouts. SFN is produced by the conversion of glucoraphanin through the enzyme myrosinase, which leads to the formation of this isothiocyanate. SFN is especially characterized by antioxidant, anti-inflammatory, and anti-apoptotic properties, and for this reason, it aroused the interest of researchers. The aim of this review is to summarize the experimental studies present on Pubmed that report the efficacy of SFN in the treatment of neurodegenerative disease, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Therefore, thanks to its beneficial effects, SFN could be useful as a supplement to counteracting neurodegenerative diseases
Activation of Nrf2 by Natural Bioactive Compounds: A Promising Approach for Stroke?
No full textStroke represents one of the main causes of disability and death worldwide. The pathological subtypes of stroke are ischemic stroke, the most frequent, and hemorrhagic stroke. Nrf2 is a transcription factor that regulates redox homeostasis. In stress conditions, Nrf2 translocates inside the nucleus and induces the transcription of enzymes involved in counteracting oxidative stress, endobiotic and xenobiotic metabolism, regulators of inflammation, and others. Different natural compounds, including food and plant-derived components, were shown to be able to activate Nrf2, mediating an antioxidant response. Some of these compounds were tested in stroke experimental models showing several beneficial actions. In this review, we focused on the studies that evidenced the positive effects of natural bioactive compounds in stroke experimental models through the activation of Nrf2 pathway. Interestingly, different natural compounds can activate Nrf2 through multiple pathways, inducing a strong antioxidant response associated with the beneficial effects against stroke. According to several studies, the combination of different bioactive compounds can lead to a better neuroprotection. In conclusion, natural bioactive compounds may represent new therapeutic strategies against stroke
The Role of Cytotoxic T-Lymphocyte Antigen 4 in the Pathogenesis of Multiple Sclerosis
No full textMultiple sclerosis (MS) is an autoimmune neurodegenerative disorder of the central nervous system that presents heterogeneous clinical manifestations and course. It has been shown that different immune checkpoints, including Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), can be involved in the pathogenesis of MS. CTLA-4 is a critical regulator of T-cell homeostasis and self-tolerance and represents a key inhibitor of autoimmunity. In this scopingreview, we resume the current preclinical and clinical studies investigating the role of CTLA-4 in MS with different approaches. While some of these studies assessed the expression levels of CTLA-4 on T cells by comparing MS patients with healthy controls, others focused on the evaluation of the effects of common MS therapies on CTLA-4 modulation or on the study of the CTLA-4 blockade or deficiency in experimental autoimmune encephalomyelitis models. Moreover, other studies in this field aimed to discover if the CTLA-4 gene might be involved in the predisposition to MS, whereas others evaluated the effects of treatment with CTLA4-Ig in MS. Although these results are of great interest, they are often conflicting. Therefore, further studies are needed to reveal the exact mechanisms underlying the action of a crucial immune checkpoint such as CTLA-4 in MS to identify novel immunotherapeutic strategies for MS patients
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