Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and glioblastoma (GBM) are characterized by complex molecular mechanisms that contribute to their pathogenesis. In ALS, a cross-ancestry genome-wide association study identified 15 risk loci associated with the disease, revealing distinct genetic architectures that include rare variants and regulatory effects (ref: van Rheenen doi.org/10.1038/s41588-021-00973-1/). This study highlights the importance of understanding genetic factors in ALS, particularly as cognitive deficits are prevalent in nearly half of ALS patients, necessitating further exploration of molecular targets like the NLRP3 inflammasome to improve therapeutic strategies (ref: Banerjee doi.org/10.1002/path.5846/). In GBM, the inhibition of LSD1 has been shown to affect tumorigenicity by deregulating the protective ATF4-dependent integrated stress response, emphasizing the need for innovative therapeutic approaches targeting tumor-initiating cells (ref: Faletti doi.org/10.1126/scitranslmed.abf7036/). Furthermore, the therapeutic potential of self-assembled siRNAs for Huntington's disease demonstrates the promise of synthetic biology in addressing neurodegenerative conditions (ref: Zhang doi.org/10.1093/brain/).

Genetic and epigenetic factors play a crucial role in various neuropathological conditions, as illustrated by several recent studies. The case of a patient developing parkinsonism after BCMA-targeting CAR-T cell therapy highlights the potential neurotoxic effects of immunotherapy, suggesting that BCMA expression on neurons may contribute to neurological complications (ref: Van Oekelen doi.org/10.1038/s41591-021-01564-7/). Additionally, the loss of APC7, a component of the E3 ubiquitin ligase, has been linked to an intellectual disability syndrome, shedding light on the molecular underpinnings of neurodevelopmental disorders (ref: Ferguson doi.org/10.1016/j.molcel.2021.11.031/). Chronic exposure to cortisol has been shown to differentially impact stem cell-derived astrocytes from patients with major depressive disorder, indicating that stress hormones can lead to significant cellular and transcriptomic changes in the brain (ref: Heard doi.org/10.1038/s41398-021-01733-9/). Furthermore, the study of DNMT1 deficiency reveals its impact on dendritic cell development, suggesting that epigenetic regulation is vital for immune responses in autoimmune diseases (ref: Czeh doi.org/10.4049/jimmunol.2100624/).

Advancements in imaging and diagnostic techniques are enhancing our understanding of neuropathology and improving clinical outcomes. A study on MRI radiomics demonstrated its potential for noninvasive prediction of BRAF mutation status in melanoma brain metastases, achieving high diagnostic performance (ref: Meißen doi.org/10.1093/neuonc/). Additionally, the clinical application of dynamic glucose enhanced imaging (GlucoCEST) in gliomas has shown promise in detecting tumor metabolism at clinical field strengths, which could aid in treatment planning (ref: Bender doi.org/10.1007/s10334-021-00982-5/). The role of advanced MRI sequences in diagnosing pituitary adenomas further underscores the importance of high-quality imaging for accurate characterization of sellar region lesions (ref: Gadelha doi.org/10.1210/clinem/). Furthermore, the correlation of imaging features with histopathological findings in CNS high-grade neuroepithelial tumors provides valuable insights into tumor biology and can guide therapeutic decisions (ref: Cardoen doi.org/10.3174/ajnr.A7367/).

Recent therapeutic approaches in neurology and oncology are yielding promising results, particularly in the context of immunotherapy and novel drug treatments. Dimethyl fumarate, an established treatment for multiple sclerosis, has been shown to alter T cell metabolism and restrict antioxidative capacities, which may influence autoimmune responses (ref: Liebmann doi.org/10.1093/brain/). In a clinical trial comparing ketamine and midazolam, mood improvement was linked to reduced suicidal ideation in patients with major depressive disorder, highlighting the rapid antidepressant effects of ketamine (ref: Hochschild doi.org/10.1016/j.jad.2021.12.055/). The identification of PD-L1 expression on platelets as a predictive marker for immunotherapy response in non-small cell lung cancer represents a significant advancement in personalized cancer treatment (ref: Hinterleitner doi.org/10.1038/s41467-021-27303-7/). Moreover, the characterization of IDH-mutant oligosarcomas as distinct and aggressive tumors emphasizes the need for tailored therapeutic strategies in neuro-oncology (ref: Suwala doi.org/10.1007/s00401-021-02395-z/).

Inflammation and immune responses are critical components in the pathology of various neurological disorders. The study of DNMT1 deficiency has revealed its significant impact on dendritic cell subsets, underscoring the role of epigenetic mechanisms in immune regulation and potential autoimmune disease development (ref: Czeh doi.org/10.4049/jimmunol.2100624/). In the context of COVID-19, research has shown that SARS-CoV-2 infection triggers profibrotic macrophage responses, contributing to lung fibrosis and highlighting the systemic effects of viral infections on immune function (ref: Wendisch doi.org/10.1016/j.cell.2021.11.033/). The integration of imaging features with histopathological data in CNS tumors further emphasizes the importance of understanding immune responses within the tumor microenvironment, which can influence treatment outcomes (ref: Cardoen doi.org/10.3174/ajnr.A7367/). These findings collectively point to the intricate interplay between inflammation, immune responses, and neuropathological conditions, necessitating further exploration to develop targeted therapies.