The novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and finding a safe therapeutic strategy and effective vaccine is critical to overcoming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, elucidation of pathogenesis mechanisms, especially entry routes of SARS-CoV-2 may help propose antiviral drugs and novel vaccines. Several receptors have been demonstrated for the interaction of spike (S) protein of SARS-CoV-2 with host cells, including angiotensin-converting enzyme (ACE2), ephrin ligands and Eph receptors, neuropilin 1 (NRP-1), P2X7, and CD147. The expression of these entry receptors in the central nervous system (CNS) may make the CNS prone to SARS-CoV-2 invasion, leading to neurodegenerative diseases. The present review provides potential pathological mechanisms of SARS-CoV-2 infection in the CNS, including entry receptors and cytokines involved in neuroinflammatory conditions. Moreover, it explains several neurodegenerative disorders associated with COVID-19. Finally, we suggest inflammasome and JaK inhibitors as potential therapeutic strategies for neurodegenerative diseases.
Innate and adaptive immune cells patrol and survey throughout the human body and sometimes reside in the tumor microenvironment (TME) with a variety of cell types and nutrients that may differ from those in which they developed. The metabolic pathways and metabolites of immune cells are rooted in cell physiology, and not only provide nutrients and energy for cell growth and survival but also influencing cell differentiation and effector functions. Nowadays, there is a growing awareness that metabolic processes occurring in cancer cells can affect immune cell function and lead to tumor immune evasion and angiogenesis. In order to safely treat cancer patients and prevent immune checkpoint blockade-induced toxicities and autoimmunity, we suggest using anti-angiogenic drugs solely or combined with Immune checkpoint blockers (ICBs) to boost the safety and effectiveness of cancer therapy. As a consequence, there is significant and escalating attention to discovering techniques that target metabolism as a new method of cancer therapy. In this review, a summary of immune-metabolic processes and their potential role in the stimulation of intracellular signaling in TME cells that lead to tumor angiogenesis, and therapeutic applications is provided.
Based on available evidence, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a neuroinvasive virus. According to the centers for disease control and prevention (CDC), coronavirus disease 2019 (COVID-19) may cause epilepsy. In this line, COVID-19 can stimulate hypoxia-inducible factor-1 alpha (HIF-1α) and activate P2X7 receptor. Both HIF-1α and P2X7 receptors are linked to epileptogenesis and seizures. Therefore, in the current study, we suggested that COVID-19 may have a role in epileptogenesis and seizure through HIF-1α stimulation and P2X7 receptor activation. Consequently, pharmacological targeting of these factors could be a promising therapeutic approach for such patients.
The Janus kinase–signal transducer and activator of transcription (JAK–STAT) pathway is involved in many immunological processes, including cell growth, proliferation, differentiation, apoptosis, and inflammatory responses. Some of these processes can contribute to cancer progression and neurodegeneration. Owing to the complexity of this pathway and its potential crosstalk with alternative pathways, monotherapy as targeted therapy has usually limited long-term efficacy. Currently, the majority of JAK–STAT-targeting drugs are still at preclinical stages. Meanwhile, a variety of plant polyphenols, especially quercetin, exert their inhibitory effects on the JAK–STAT pathway through known and unknown mechanisms. Quercetin has shown prominent inhibitory effects on the JAK–STAT pathway in terms of anti-inflammatory and antitumor activity, as well as control of neurodegenerative diseases. This review discusses the pharmacological effects of quercetin on the JAK–STAT signaling pathway in solid tumors and neurodegenerative diseases.
The permeability of glioblastoma, as well as its escaping the immune system, makes them one of the most deadly human malignancies. By avoiding programmed cell death (apoptosis), unlimited cell growth and metastatic ability could dramatically affect the immune system. Genetic mutations, epigenetic changes, and overexpression of oncogenes can cause this process. On the other hand, the blood-brain barrier (BBB) and intratumor heterogeneity are important factors causing resistance to therapy. Several signaling pathways have been identified in this field, including the Janus tyrosine kinase (JAK) converter and signal transducer and activator of transcription (STAT) activator pathways, which are closely related. In addition, the JAK/STAT signaling pathway contributes to a wide array of tumorigenesis functions, including replication, anti-apoptosis, angiogenesis, and immune suppression. Introducing this pathway as the main tumorigenesis and treatment resistance center can give a better understanding of how it operates. In light of this, it is an important goal in treating many disorders, particularly cancer. The inhibition of this signaling pathway is being considered an approach to the treatment of glioblastoma. The use of natural products alternatively to conventional therapies is another area of research interest among researchers. Some natural products that originate from plants or natural sources can interfere with JAK/STAT signaling in human malignant cells, also by stopping the progression and phosphorylation of JAK/STAT, inducing apoptosis, and stopping the cell cycle. Natural products are a viable alternative to conventional chemotherapy because of their cost-effectiveness, wide availability, and almost no side effects.
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