Recent studies have highlighted the role of immunomodulation in neuroinflammatory conditions such as multiple sclerosis (MS) and traumatic brain injury (TBI). For instance, Duscha et al. demonstrated that propionic acid (PA), a short-chain fatty acid, can significantly influence the disease course in therapy-naive MS patients by normalizing Treg cell mitochondrial function, suggesting its potential as an adjunct to MS therapies (ref: Duscha doi.org/10.1016/j.cell.2020.02.035/). In TBI, Willis et al. found that repopulating microglia, induced through pharmacological or genetic means, can promote brain repair in an IL-6-dependent manner, enhancing neurogenesis and cognitive recovery (ref: Willis doi.org/10.1016/j.cell.2020.02.013/). Additionally, Di Sante et al. explored the effects of the S100B inhibitor pentamidine in a relapsing-remitting MS mouse model, revealing that it can delay disease progression and improve clinical scores, indicating a promising therapeutic avenue (ref: Di Sante doi.org/10.3390/cells9030748/). Chronic peripheral inflammation was shown by Süß et al. to induce a region-specific myeloid response in the central nervous system, underscoring the complexity of immune interactions in neuroinflammatory contexts (ref: Süß doi.org/10.1016/j.celrep.2020.02.109/). Furthermore, Schottlaender et al. identified bi-allelic JAM2 variants linked to early-onset primary familial brain calcification, adding to the genetic landscape of neuroinflammatory disorders (ref: Schottlaender doi.org/10.1016/j.ajhg.2020.02.007/).

The search for reliable biomarkers in Alzheimer's disease (AD) has gained momentum, particularly with the identification of plasma P-tau181 as a significant indicator of AD pathology. Janelidze et al. reported that plasma P-tau181 can differentiate AD dementia from non-AD neurodegenerative diseases with high accuracy (AUC = 0.94-0.98), and its levels correlate with the development of AD dementia in cognitively unimpaired individuals (ref: Janelidze doi.org/10.1038/s41591-020-0755-1/). Ranasinghe et al. further elucidated the neurophysiological signatures associated with tau and amyloid-β accumulation, revealing that alpha hyposynchrony is closely linked to tau deposition and cognitive decline, while delta-theta hypersynchrony correlates with both tau and amyloid-β (ref: Ranasinghe doi.org/10.1126/scitranslmed.aaz4069/). Dhiman et al. demonstrated that cerebrospinal fluid neurofilament light (NfL) levels predict brain atrophy and cognitive decline in AD, reinforcing its role as a neurodegeneration biomarker (ref: Dhiman doi.org/10.1002/dad2.12005/). Amadoru et al. compared amyloid PET results with neuropathological findings, establishing Centiloid thresholds that correlate with clinical diagnoses of AD (ref: Amadoru doi.org/10.1186/s13195-020-00587-5/). Lastly, Mashkaryan et al. explored the role of IL-4 signaling in promoting neurogenesis, suggesting potential therapeutic strategies targeting glial proliferation in AD (ref: Mashkaryan doi.org/10.3389/fcell.2020.00114/).

Genetic factors play a crucial role in neurodegenerative diseases, as evidenced by recent findings linking specific mutations to conditions such as Parkinson's disease and Alzheimer's disease. Oji et al. identified pathogenic mutations in the saposin D domain of the prosaposin gene in families with autosomal dominant Parkinson's disease, providing new insights into the genetic underpinnings of this condition (ref: Oji doi.org/10.1093/brain/). In the context of amyotrophic lateral sclerosis (ALS), Nabais et al. utilized DNA methylation profiling to classify cases and controls, revealing significant out-of-sample classification capabilities that could enhance diagnostic accuracy (ref: Nabais doi.org/10.1038/s41525-020-0118-3/). Lüningschrör et al. investigated the FTLD risk factor TMEM106B, demonstrating its role in lysosomal transport and its implications for neurodegenerative processes (ref: Lüningschrör doi.org/10.1016/j.celrep.2020.02.060/). Lim et al. focused on hematopoietic cell kinase (HCK) and its impact on microglial function and amyloid-β clearance in Alzheimer's disease models, suggesting that HCK loss accelerates neuropathology (ref: Lim doi.org/10.1007/s12035-020-01894-6/). Lastly, Niesen et al. explored the effects of Pik3ca mutations on medulloblastoma growth, highlighting the genetic complexity of brain tumors (ref: Niesen doi.org/10.1016/j.canlet.2020.02.028/).

Neurodevelopmental disorders and brain tumors present unique challenges in understanding their biological underpinnings and therapeutic approaches. Hoffman et al. discussed the molecular heterogeneity of atypical teratoid rhabdoid tumors (ATRT), emphasizing the need for biology-based therapeutic strategies in light of recent genomic analyses that reveal complexity beyond the previously assumed monogenic nature of these tumors (ref: Hoffman doi.org/10.1093/neuonc/). Davies et al. recapitulated the EEF1A2 D252H mutation in mice, shedding light on the toxic gain of function associated with neurodevelopmental disorders linked to this gene, which could inform future therapeutic strategies (ref: Davies doi.org/10.1093/hmg/). García-Arriaza et al. investigated tau immunotherapy in a P301S mouse model of Alzheimer's disease, highlighting the potential of vaccination strategies to mitigate tau pathology (ref: García-Arriaza doi.org/10.3390/vaccines8010127/). Anghileri et al. conducted a large retrospective analysis of gliomatosis cerebri, identifying key prognostic factors that could guide treatment decisions (ref: Anghileri doi.org/10.1007/s10072-020-04288-7/). Lastly, Friedrich et al. examined the immune activation mechanisms of the VSV-EBOV vaccine, which could have implications for vaccine development in neuro-oncology (ref: Friedrich doi.org/10.3390/vaccines8010142/).

Microglial function and neurogenesis are critical areas of research in understanding brain repair mechanisms and neurodegenerative diseases. Willis et al. demonstrated that repopulating microglia can promote brain repair following traumatic brain injury through IL-6-dependent mechanisms, enhancing the survival of newborn neurons and supporting cognitive function (ref: Willis doi.org/10.1016/j.cell.2020.02.013/). Lüningschrör et al. further explored the role of TMEM106B in lysosomal transport, revealing its significance in the regulation of microglial function and implications for neurodegeneration (ref: Lüningschrör doi.org/10.1016/j.celrep.2020.02.060/). Süß et al. provided insights into how chronic peripheral inflammation induces heterogeneous myeloid responses across different brain regions, which could influence neuroinflammatory processes and neurogenesis (ref: Süß doi.org/10.1016/j.celrep.2020.02.109/). Additionally, Eckermann et al. developed a novel phase-contrast x-ray tomography technique to visualize neuronal tissue, potentially aiding in the study of microglial interactions and neurogenesis at high resolution (ref: Eckermann doi.org/10.1117/1.JMI.7.1.013502/).

Mitochondrial dysfunction has emerged as a key player in various neuropathological conditions, influencing disease progression and therapeutic outcomes. Schöpf et al. highlighted the role of mitochondrial DNA mutations in prostate cancer, linking these alterations to energy metabolism rewiring and suggesting that such mutations may serve as biomarkers for disease risk (ref: Schöpf doi.org/10.1038/s41467-020-15237-5/). Ozawa et al. investigated the DJ-1 gene, known for its association with familial Parkinson's disease, revealing that its deletion impairs S-nitrosylation of Parkin, leading to mitochondrial dysfunction and increased cell death under stress conditions (ref: Ozawa doi.org/10.1038/s41598-020-61287-6/). Lüningschrör et al. also contributed to this theme by demonstrating how TMEM106B affects lysosomal transport, which is crucial for maintaining mitochondrial health and function (ref: Lüningschrör doi.org/10.1016/j.celrep.2020.02.060/). Wollborn et al. explored the neuroprotective effects of carbon monoxide in a cardiac arrest model, showing that it can reduce neurological damage and improve mitochondrial function post-resuscitation (ref: Wollborn doi.org/10.1097/CCM.0000000000004242/).

The intersection of cancer and neuropathology presents unique challenges and opportunities for therapeutic advancements. Hoffman et al. discussed the molecular heterogeneity of atypical teratoid rhabdoid tumors (ATRT), emphasizing the need for biology-based therapeutic strategies in light of recent genomic analyses that reveal complexity beyond the previously assumed monogenic nature of these tumors (ref: Hoffman doi.org/10.1093/neuonc/). Heaphy et al. investigated telomere length alterations in pituitary adenomas, revealing significant variations that correlate with clinicopathological characteristics, which could inform prognostic assessments (ref: Heaphy doi.org/10.1038/s41379-020-0523-2/). Niesen et al. explored the impact of Pik3ca mutations on the growth of Sonic hedgehog medulloblastoma, highlighting the genetic factors that contribute to tumor aggressiveness and metastasis (ref: Niesen doi.org/10.1016/j.canlet.2020.02.028/). Nabais et al. conducted DNA methylation association analyses in ALS, providing insights into the epigenetic landscape of neurodegenerative diseases and their potential overlap with cancer biology (ref: Nabais doi.org/10.1038/s41525-020-0118-3/).