Logo: to the web site of Uppsala University

Progressive neurodegenerative diseases (NDs) that lack effective disease-modifying treatments, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), represent significant global health challenges. In recent years, key research findings have included the role of neuroinflammation driven by microglia and astrocytes, the impact of genetic mutations, and the importance of autophagy and mitochondrial quality control in maintaining neuronal health. In this review, we summarize recent advancements of the pathogenesis of NDs, the cellular and animal models that have provided valuable insights into disease mechanisms, and the development of blood-based biomarkers for early diagnosis and monitoring of disease progression. We also highlight emerging neurorestorative therapeutic strategies involving stem cell therapy, antisense oligonucleotides, and induced pluripotent stem cells. Additionally, we cover recent clinical trials of promising drugs, such as lecanemab and donanemab for AD, and tavapadon for PD. Finally, we propose future research directions, emphasizing the need for combination therapies that target multiple pathways, the development of more precise animal models, and the integration of nanotechnology for improved drug delivery across the blood–brain barrier.

Introduction: Glioblastoma (GB) is one of the deadliest human brain tumors. The prognosis is unfavorable, chemotherapy with temozolomide (TMZ) may extend the survival period for a patient. The paper aims to evaluate the survival rates among relapsing GB patients, who have been treated with valproic acid (VPA), and to study its effect on tumor cells when combined with TMZ and celecoxib (CXB).

Materials and Methods: The research is based on retrospective analysis of the data from GB patients who had been treated with VPA as a part of a complex treatment protocol and reoperated due to a GB relapse. The experimental study involved cancer cells of C6, U87, and T98G lines. GB was modeled on Wistar rats. The research was approved by the ethics committee. Differences in groups were considered significant at p < 0.05 Results: The median of overall survival among GB patients who took VPA was 22 months, and for those who did not take VPA - 13 months. The in vitro experiment showed the half-maximal inhibitory concentration (IC50) of TMZ for various lines of cancer cells (CCs) varying from 435.3 to 844 mu M. IC50 VPA for CCs of U87MG, T98G, and & Scy;6 lines was 1510, 3900, and 3600 mu M: IC50 CXB for those lines of CCs was 30.1 mu M, 41.07, and 48.4 mu M respectively. VPA significantly enhanced the anti-glioma effect of TMZ on the U87 line of CCs, while CCs of C6 and T98G lines proved to be most susceptible to the combination of CXB and TMZ. The combination of VPA with CXB increased the anti-glioma effect of TMZ both in vitro and in vivo, also reducing the tumor size (& rcy; < 0.05) and prolonging the survival period among experimental animals.

Results: The median of overall survival among GB patients who took VPA was 22 months, and for those who did not take VPA - 13 months. The in vitro experiment showed the half-maximal inhibitory concentration (IC50) of TMZ for various lines of cancer cells (CCs) varying from 435.3 to 844 mu M. IC50 VPA for CCs of U87MG, T98G, and & Scy;6 lines was 1510, 3900, and 3600 mu M: IC50 CXB for those lines of CCs was 30.1 mu M, 41.07, and 48.4 mu M respectively. VPA significantly enhanced the anti-glioma effect of TMZ on the U87 line of CCs, while CCs of C6 and T98G lines proved to be most susceptible to the combination of CXB and TMZ. The combination of VPA with CXB increased the anti-glioma effect of TMZ both in vitro and in vivo, also reducing the tumor size (& rcy; < 0.05) and prolonging the survival period among experimental animals.

Conclusion: VPA and CXB enhance the effect of TMZ on glioblastoma cells.

Remarkable advancements have been made in understanding the pathogenesis of Alzheimer's disease, Parkinson's disease, and other neurological disease; in our depth of understanding neurorestorative mechanisms such as anti-inflammatory processes, immune regulation, neuromodulation, neovascularization/neural repair, and neuroprotection; and in clinical neurorestorative treatments. Multiple types of cell therapies have been reported, with some positive outcomes. Diverse forms of neurostimulation and neuromodulation as well as brain-computer interfaces have shown good therapeutic outcomes in clinical applications. Further, therapeutic neurorestorative surgery and pharmaceutic therapy have been very impressive. These fundamental achievements are helpful for understanding the pathogenesis of neurological diseases and the mechanisms of neurorestoration. Patients with neurological impairments have benefited from therapeutic progress, but some of these therapies still require confirmation in higher-level randomized clinical trials.