Expert Opinion on Therapeutic Targets最新文献

Introduction: Longevity research has matured to the point where significantly postponing age-related decline in physical and mental function is now achievable in the laboratory and foreseeable in the clinic. The most promising strategies involve rejuvenation, i.e. reducing biological age, not merely slowing its progression.

Areas covered: We discuss therapeutic strategies for rejuvenation and results achieved thus far, with a focus on in vivo studies. We discuss the implications of interventions which act on mean or maximum lifespan and those showing effects in accelerated disease models. While the focus is on work conducted in mice, we also highlight notable insights in the field from studies in other model organisms.

Expert opinion: Rejuvenation was originally proposed as easier than slowing aging because it targets initially inert changes to tissue structure and composition, rather than trying to disentangle processes that both create aging damage and maintain life. While recent studies support this hypothesis, a true test requires a panel of rejuvenation interventions targeting multiple damage categories simultaneously. Considerations of cost, profitability, and academic significance have dampened enthusiasm for such work, but it is vital. Now is the time for the field to take this key step toward the medical control of aging.

Introduction: Collagen triple helix repeat containing 1 (CTHRC1) is a protein that has been implicated in pro-migratory pathways, arterial tissue-repair processes, and inhibition of collagen deposition via the regulation of multiple signaling cascades. Studies have also demonstrated an upregulation of CTHRC1 in multiple cancers where it has been linked to enhanced proliferation, invasion, and metastasis. However, the understanding of the exact role and mechanisms of CTHRC1 in cancer is far from complete.

Areas covered: This review focuses on analyzing the role of CTHRC1 in cancer as well as its associations with clinicopathologies and cancer-related processes and signaling. We have also summarized the available literature information regarding the role of CTHRC1 in tumor microenvironment and immune signaling. Finally, we have discussed the mechanisms associated with CTHRC1 regulations, and opportunities and challenges regarding the development of CTHRC1 as a potential target for cancer management.

Expert opinion: CTHRC1 is a multifaceted protein with critical roles in cancer progression and other pathological conditions. Its association with lower overall survival in various cancers, and impact on the tumor immune microenvironment make it an intriguing target for further research and potential therapeutic interventions in cancer.

Introduction: Inflammasome complexes, especially NLRP3, have gained great attention as a potential therapeutic target in mood disorders. NLRP3 triggers a caspase 1-dependent release of the inflammatory cytokines IL-1β and IL-18, and seems to interact with purinergic and kynurenine pathways, all of which are implicated in mood disorders development and progression.

Areas covered: Emerging evidence supports NLRP3 inflammasome as a promising pharmacological target for mood disorders. We discussed the available evidence from animal models and human studies and provided a reflection on drawbacks and perspectives for this novel target.

Expert opinion: Several studies have supported the involvement of NLRP3 inflammasome in MDD. However, most of the evidence comes from animal models. The role of NLRP3 inflammasome in BD as well as its anti-manic properties is not very clear and requires further exploration. There is evidence of anti-manic effects of P2×R7 antagonists associated with reduction in the brain levels of IL-1β and TNF-α in a murine model of mania. The involvement of other NLRP3 inflammasome expressing cells besides microglia, like astrocytes, and of other inflammasome complexes in mood disorders also deserves further investigation. Preclinical and clinical characterization of NLRP3 and other inflammasomes in mood disorders is needed before considering translational approaches, including clinical trials.

Introduction: HIF-1α, a key player in medical science, holds immense significance in therapeutic approaches. This review delves into its complex dynamics, emphasizing the delicate balance required for its modulation. HIF-1α stands as a cornerstone in medical research, its role extending to therapeutic strategies. This review explores the intricate interplay surrounding HIF-1α, highlighting its critical involvement and the necessity for cautious modulation.

Areas covered: In sickle cell disease (SCD), HIF-1α's potential to augment fetal hemoglobin (HbF) production and mitigate symptoms is underscored. Furthermore, its role in cancer is examined, particularly its influence on survival in hypoxic tumor microenvironments, angiogenesis, and metastasis. The discussion extends to the intricate relationship between HIF-1α modulation and cancer risks in SCD patients, emphasizing the importance of balancing therapeutic benefits and potential hazards.

Expert opinion: Managing HIF-1α modulation in SCD patients requires a nuanced approach, considering therapeutic potential alongside associated risks, especially in exacerbating cancer risks. An evolutionary perspective adds depth, highlighting adaptations in populations adapted to low-oxygen environments and aligning cancer cell metabolism with primitive cells. The role of HIF-1α as a therapeutic target is discussed within the context of complex cancer biology and metabolism, acknowledging varied responses across diverse cancers influenced by intricate evolutionary adaptations.

Introduction: Mayaro fever is an emerging viral disease that manifests as an acute febrile illness. The disease is self-limiting, however joint pain can persist for months leading to chronic arthralgia. There is no specific treatment available, which ultimately leads to socioeconomic losses in populations at risk as well as strains to the public health systems.

Areas covered: We reviewed the candidate treatments proposed for Mayaro virus (MAYV) infection and disease, including antiviral compounds targeting viral or host mechanisms, and pathways involved in disease development and pathogenicity. We assessed compound screening technologies and experimental infection models used in these studies and indicated the advantages and limitations of available technologies and intended therapeutic strategies.

Expert opinion: Although several compounds have been suggested as candidate treatments against MAYV infection, notably those with antiviral activity, most compounds were assessed only in vitro. Compounds rarely progress toin vivo or preclinical studies, and such difficulty may be associated with limited experimental models. MAYV biology is largely inferred from related alphaviruses and reflected by few studies focusing on target proteins or mechanisms of action for MAYV. Therapeutic strategies targeting pathogenic inflammatory responses have shown potential against MAYV-induced disease in vivo, which might reduce long-term sequelae.