Parkinson’s disease (PD) is a complex neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra and the widespread accumulation of alpha-synuclein (αSyn) protein aggregates. αSyn aggregation disrupts critical cellular processes, including synaptic function, mitochondrial integrity, and proteostasis, which culminate in neuronal cell death. Importantly, αSyn pathology extends beyond neurons—it also encompasses spreading throughout the neuronal environment and internalization by microglia and astrocytes. Once internalized, glia can act as neuroprotective scavengers, which limit the spread of αSyn. However, they can also become reactive, thereby contributing to neuroinflammation and the progression of PD. Recent advances in αSyn research have enabled the molecular diagnosis of PD and accelerated the development of targeted therapies. Nevertheless, despite more than two decades of research, the cellular function, aggregation mechanisms, and induction of cellular damage by αSyn remain incompletely understood. Unraveling the interplay between αSyn, neurons, and glia may provide insights into disease initiation and progression, which may bring us closer to exploring new effective therapeutic strategies. Herein, we provide an overview of recent studies emphasizing the multifaceted nature of αSyn and its impact on both neuron and glial cell damage.

Head and neck cancer (HNC) is a prevalent and diverse group of malignancies with substantial morbidity and mortality rates. Early detection and monitoring of HNC are crucial for improving patient outcomes. Liquid biopsy, a non-invasive diagnostic approach, has emerged as a promising tool for cancer detection and monitoring. In this article, we review the application of RNA-based liquid biopsy in HNC. Various types of RNA, including messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), circular RNA (circRNA) and PIWI-interacting RNA (piRNA), are explored as potential biomarkers in HNC liquid-based diagnostics. The roles of RNAs in HNC diagnosis, metastasis, tumor resistance to radio and chemotherapy, and overall prognosis are discussed. RNA-based liquid biopsy holds great promise for the early detection, prognosis, and personalized treatment of HNC. Further research and validation are necessary to translate these findings into clinical practice and improve patient outcomes.

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, although the aetiology of ADHD is not yet understood. One proposed theory for developing ADHD is N-methyl-D-aspartate receptors (NMDARs) dysfunction. NMDARs are involved in regulating synaptic plasticity and memory function in the brain. Abnormal expression or polymorphism of some genes associated with ADHD results in NMDAR dysfunction. Correspondingly, NMDAR malfunction in animal models results in ADHD-like symptoms, such as impulsivity and hyperactivity. Currently, there are no drugs for ADHD that specifically target NMDARs. However, NMDAR-stabilizing drugs have shown promise in improving ADHD symptoms with fewer side effects than the currently most widely used psychostimulant in ADHD treatment, methylphenidate. In this review, we outline the molecular and genetic basis of NMDAR malfunction and how it affects the course of ADHD. We also present new therapeutic options related to treating ADHD by targeting NMDAR.

Multiple sclerosis (MS) is a chronic, autoimmune neurodegenerative disease affecting the central nervous system. It is a major cause of non-traumatic neurological disability among young adults in North America and Europe. This study focuses on neuroprotective genes (BDNF, NT4/5, SIRT1, HSP70, and HSP27). Gene expression and protein levels of these markers were compared between MS patients and healthy controls. Blood samples were collected from 42 patients with multiple sclerosis (MS) and 48 control subjects without MS. Quantitative real-time PCR was performed to measure the expression of specific genes. The samples were analyzed in duplicate, and the abundance of mRNA was quantified using the 2-ΔCt method. ELISA assay was used to measure the concentration of specific proteins in the plasma samples. The results show that a 3.5-fold decrease in the gene expression of BDNF corresponds to a 1.5-fold downregulation in the associated plasma protein concentration (p < 0.001). Similar trends were observed with NT-4 (five-fold decrease, slight elevation in protein), SIRT1 (two-fold decrease, two-fold protein decrease), HSP70 (four-fold increase, nearly two-fold protein increase), and HSP27 (four-fold increase, two-fold protein increase) (p < 0.001). This study reveals strong correlations between gene expression and protein concentration in MS patients, emphasizing the relevance of these neuroprotective markers in the disease.

Rheumatoid arthritis (RA) is a chronic, common autoimmune disease. It is characterized by inflammatory polyarthritis, which can lead to permanent disability in patients. Current treatment is mainly symptom-related, aiming to reduce pain and inflammation, but does not lead to a full recovery. This treatment includes non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs). It has been shown that, due to chronic inflammation, reduced glucose levels and hypoxia, endoplasmic reticulum (ER) stress is induced in RA patients, leading to the activation of multiple signaling pathways, including the ER-dependent adaptation of the unfolded protein response (UPR) pathway. The aim of this study was to assess the level of apoptosis in patients diagnosed with RA. The study sought to investigate whether UPR response correlated with apoptosis induction could serve as a potential diagnostic marker or therapeutic target. In vitro studies have shown that UPR pathway activity can be observed in patients diagnosed with RA. The study group consisted of PBMC cells from 61 individuals, including a total of 31 rheumatoid arthritis patients and 30 healthy controls. In order to validate UPR activation, we estimated molecular markers of ER stress via RT-qPCR expression analysis. GAPDH expression was used as a standard control. Elevated levels of mRNA for the eIF2α (p-value = 0.001903), the BBC3 (PUMA) (p-value = 0.007457 × 10⁻⁷) and the TP53 (p-value = 0.002212) were confirmed in a group of RA patients. Further analysis showed that after the induction of apoptosis the percentage of DNA contained in the tail was 37.78% higher in RA patients than in the control group (p-value = 0.0003) measured by comet assay. The exogenous damage caused by hydrogen peroxide was found to be statistically elevated in RA patients and the caspase-3 level was calculated of 40.17% higher than in controls (p-value = 0.0028). It was also found that PBMC cells from RA patients were more sensitive to apoptotic induction. Our results were confirmed by flow cytometry. The most important finding from our data was the confirmation of elevated sensitivity to apoptosis induction in RA patients; the results showed a 40.23% higher percentage of cells in early apoptosis than in the control group (p-value = 0.0105). Our results may help to assess the feasibility of the application of early diagnosis and targeted therapy in the treatment of RA patients, including the ER signaling pathway via selected UPR-dependent molecular inhibitors.

Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by immune-mediated inflammation and neurodegeneration in the central nervous system (CNS). In this study; we aimed to investigate the gene expression and plasma protein levels of three neuroprotective genes—heat shock proteins (HSP90 and HSP60) and glial cell line-derived neurotrophic factor (GDNF)—in MS patients compared to healthy controls. Forty patients with relapsing-remitting MS and 40 healthy volunteers participated in this study. Gene expression was measured using reverse transcription quantitative real-time PCR, and protein levels were assessed via ELISA. The results showed a significant increase in HSP90 (1.7-fold) and HSP60 (2-fold) gene expression in MS patients compared to controls, along with corresponding increases in protein levels (1.5-fold for both HSP90 and HSP60). In contrast, GDNF gene expression and protein levels were significantly reduced in MS patients, with a 7-fold decrease in gene expression and a 1.6-fold reduction in protein levels. Notably, a non-linear relationship between GDNF gene expression and protein concentration was observed in MS patients, suggesting complex regulatory mechanisms influencing GDNF in the disease. The upregulation of HSP90 and HSP60 in MS highlights their roles in immune regulation and stress responses, while the reduction in GDNF indicates impaired neuroprotection. These findings suggest that HSP90, HSP60, and GDNF could serve as biomarkers for disease progression and as potential therapeutic targets in MS, offering promising avenues for future research and treatment development.