Alzheimer’s disease (AD) is a chronic neurodegenerative disorder with declining memory and cognitive impairment, largely mediated by extracellular amyloid-beta (Aβ). Although the amyloid cascade and tau protein hypotheses have long served as established frameworks for AD pathology, recent evidence suggests that long-term infections, particularly with Chlamydia pneumoniae (C. pneumoniae), may contribute to disease progression. A systematic search strategy was used to identify relevant literature using PubMed, Scopus, Google Scholar, and Web of Science. Keywords and Boolean operators such as “Chlamydia pneumoniae and Alzheimer’s disease,” “neuroinflammation,” “amyloid-beta,” and “tau protein” were applied, with filters for peer-reviewed articles, human and experimental studies, and publications from the past 25 years. Epidemiological and background data were supplemented by official sources, including the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO). This review examines the potential relationship of C. pneumoniae infection with AD pathogenesis. Studies have identified DNA and antigens of C. pneumoniae in AD-infected brain regions, often co-localized within Aβ plaques and neurofibrillary tangles (NFTs). Proposed mechanisms of CNS invasion include olfactory, hematogenous, and immune cell-mediated routes, leading to persistent glial activation, neuroinflammation, altered amyloid precursor protein processing, and tau protein hyperphosphorylation. Experimental models support these associations, with infected animals developing AD-like pathology. Diagnostic challenges persist due to the limitations of PCR and immunohistochemistry, though advanced approaches such as next-generation sequencing and TSPO-PET imaging are emerging. Potential therapeutic approaches include antimicrobial and immunomodulatory strategies, although human trials have shown mixed results. While current evidence suggests a possible link, causality remains unproven. Future research must prioritize large-scale, longitudinal, and mechanistic studies to clarify these relationships. Establishing a definitive role for C. pneumoniae in AD pathogenesis could reshape current understanding of disease etiology and inform the development of novel preventive and therapeutic strategies.

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Recent progress in translational neuroscience has significantly advanced our understanding of neurological diseases. Research progress closely went in line with innovations in research methods, which have expanded our insights considerably beyond previous limits. However, despite the development of disease-modifying treatments, therapeutic options in brain diseases still lag behind fundamental discoveries in basic neuroscience. This perspective examines the factors that hinder clinical progress in translational neuroscience and provides solutions on how to overcome them. Editorial board members of Exploration of Neuroscience were interrogated about the most prominent challenges they see in translational neuroscience and about possible ways to overcome these issues. Key challenges were seen at the interface between experimental research and clinical studies by several members, both from the basic and applied neuroscience fields, which include the selection of appropriate study readouts and endpoints. The establishment of refined study endpoints, combined with biomarkers capable of predicting treatment responses in human patients, will be crucial for the successful clinical implementation of new therapies. Further obstacles were found in the standardization of experimental models, interventions, and assessments both in animals and humans, as well as in the development of personalized treatment strategies. These challenges can be addressed through more clearly defined experimental procedures that closely match clinical conditions and precision-based approaches that ensure efficient therapeutic responses. As a great opportunity, treatment options targeting pathophysiological processes in multiple brain diseases and disease processes in different organ systems were noted. Significant barriers remain in the funding of investigator-driven clinical trials through public research programs, as well as the education of translational and clinician scientists dedicated to clinical translation. Enhanced communication between experimental neuroscientists and clinicians, with a shared understanding and common language, will be essential for the success of future research endeavors.

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Treatment resistant depression (TRD) is frequently encountered in clinical practice. The lack of response of the condition to conventional medications and augmentation strategies has spawned the search for novel treatment approaches. Psychedelic medications used in conjunction with intensive psychotherapy, so-called psychedelic-assisted psychotherapy (PAP), have been evaluated in a limited number of studies as an alternative tactic. This psychedelic renaissance has seen psilocybin, a naturally occurring, potentially hallucinogenic substance occurring in some species of mushrooms, used as one exemplar. The definition of “treatment resistance” varies between different authorities, but there is general agreement that a minimum standard is failure to respond to at least two pharmacological agents from different classes used at a therapeutic dose for an adequate length of time. In the studies to date, more stringent definitions have mostly been applied. Each of the clinical evaluations finds that the addition of a single dose of psilocybin to the psychotherapeutic regimen produces a rapid and clinically significant decline in depressive symptomatology, which is mostly retained in follow-up evaluations out to 12 weeks or longer. Psilocybin was well tolerated with mostly mild to moderate side effects of elevated blood pressure, fatigue, lack of concentration, headache, lethargy, vertigo, feeling of physical or emotional weakness, decreased appetite, nausea, feeling dull, and being easily exhausted, which were transient. Hallucinogen persisting perception disorder (HPPD) has occasionally been reported, while there were few reports of suicidal ideation and behaviour. Psilocybin appears to offer the promise of rapid alleviation of resistant depressive symptoms, but further controlled evaluations are necessary before the drug can be given routinely.

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Down syndrome (DS), caused by trisomy 21, is strongly associated with an increased risk of early-onset Alzheimer’s disease (AD). This work explores the cellular, genetic, epigenetic, and neuropsychological mechanisms that underlie the accelerated development of AD in individuals with DS. We review key contributors such as amyloid-β accumulation, mitochondrial dysfunction, oxidative stress, tau pathology, neuroinflammation, and chromosomal and epigenetic instability in the neuropathology of AD in DS. Particular attention is given to genes, microRNAs, and chromatin remodeling factors encoded by human chromosome 21 (Hsa21) that regulate these pathological processes. We also highlight the roles of non-coding RNAs and altered DNA methylation patterns in modulating gene expression and neuronal vulnerability. Additionally, the writing evaluates current pharmacological and non-pharmacological interventions and addresses the critical need for inclusive, person-centered health services. Integrating molecular biology with clinical perspectives, the review emphasizes the importance of early diagnosis and coordinated care strategies for individuals with DS at risk for AD.

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Mucopolysaccharidosis type IIIB (MPS IIIB), or Sanfilippo Syndrome type B, is a lysosomal storage disorder caused by mutations in the NAGLU gene, which encodes the enzyme alpha-N-acetylglucosaminidase, responsible for the degradation of heparan sulfate. Progressive accumulation of undegraded glycosaminoglycans primarily affects the central nervous system, resulting in severe neurodegeneration. Cellular findings reveal impaired intracellular trafficking, especially within the Golgi apparatus, linked to GM130 depletion and accumulation of GM2 and GM3 gangliosides. Endocytic vesicles fail to properly fuse with lysosomes due to genetic defects, disrupting lysosomal degradation. This contributes to oxidative stress, mitochondrial dysfunction, and mitophagy failure, which collectively drive neuronal apoptosis. MPS IIIB shares pathways with Alzheimer’s and Parkinson’s, suggesting cellular aging processes. Given the lack of specific treatment, modulation of inflammatory pathways such as TLR4 emerges as a potential therapeutic strategy.

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Neurofibromatosis type 1 (NF1) is a hereditary, autosomal dominant condition marked by the development of tumors along the nervous system due to uncontrolled cell proliferation. The current case reports a 31-year-old male patient diagnosed with NF1 with the involvement of bilateral pheochromocytomas and colonic inflammatory polyps/leiomyoma. A genetic profile was explored through whole-exome sequencing to identify pathogenic variants, and segregation analysis was subsequently performed in the patient’s family. Sequencing analysis revealed a novel heterozygous frameshift variant, NF1 c.7301dupA (p.S2435Efs*11), which was identified as the pathogenic variant in the patient. Additionally, two identified variants, PMS2 c.2T>C (p.M1T) and MUTYH c.850-2A>G, may be associated with colonic tumor conditions in the patient. These findings provide insights into the molecular etiology underlying this rare presentation of multiple tumors in a Vietnamese male and may contribute to improved treatment planning and patient management.

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Congenital hydrocephalus (CH) is an extreme cerebrospinal fluid (CSF) condition that affects brain development. Current medical treatments, such as ventriculoperitoneal shunting and endoscopic third ventriculostomy, are invasive and susceptible to complications. The subventricular zone (SVZ) is involved in CH, but investigations are hindered by conventional models. Here, we introduce SVZonChip, a dynamic 3D microfluidic device simulating SVZ physiology and CSF dynamics, presenting a proof-of-concept system that could be applied for studying CH. This bioengineered device provides a translational bridge between disease modeling and therapeutic discovery, opening up avenues for non-invasive treatments.

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Parkinson’s disease is typified by Lewy bodies and the selective death of dopaminergic neurons in the substantia nigra. α-Synuclein aggregation, neuroinflammation, mitochondrial dysfunction, and oxidative stress are key components of its pathophysiology. The neuroprotective potential of natural substances with anti-inflammatory and antioxidant qualities has drawn attention in recent years. A naturally occurring isoflavone that is mostly present in red clover and other legumes, biochanin A has shown promise as a treatment option for Parkinson’s disease. Preclinical research has shown that biochanin A uses a variety of methods to provide notable neuroprotective benefits. By activating the Nrf2/ARE pathway, it scavenges reactive oxygen species (ROS), upregulates antioxidant defense enzymes, and inhibits pro-inflammatory mediators by modifying the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling cascade. Additionally, it has been demonstrated that biochanin A preserves neuronal integrity in Parkinson’s disease models by reducing dopaminergic neuronal death, inhibiting microglial activation, and mitigating mitochondrial dysfunction. Its potential as a neurotherapeutic agent is increased by its capacity to pass the blood-brain barrier. To investigate its safety, bioavailability, and effectiveness in people, more translational and clinical research is necessary. Biochanin A’s incorporation with neuroprotective techniques may pave the way for novel supplementary treatments for Parkinson’s disease. Therefore, the current review aims to present a thorough investigation of the molecular basis of biochanin A’s anti-Parkinson properties in Parkinson’s disease, building on the body of existing research that explains these properties.

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common type of dementia, characterized by cognitive decline in later years of life. Among various hypotheses explaining AD pathology, the cholinergic hypothesis is one of the most studied. Though there are Food and Drug Administration (FDA) approved drugs (donepezil, galantamine, rivastigmine and tacrine) for AD treatment, their adverse effects make it urgent to develop new drugs with minimal side effects. This review focuses on the acetylcholinesterase (AChE) inhibitory potential of plant extracts and phytochemicals that could aid in preventing and mitigating AD. From the literature search, extracts of 28 species were found to have strong inhibition against AChE, with IC₅₀ values ranging from 0.08 μg/mL to 10.0 μg/mL. The highest number of species with AChE inhibition belongs to the Amaryllidacea family, followed by Fabaceae, Lycopodiaceae, Amaranthaceae and Anacardiaceae. Several phytochemicals, including alkaloids, terpenoids and phenolics, show a multitarget approach in AD therapy, exhibiting more than one of the following activities such as inhibition of AChE, butyrylcholinesterase (BuChE), MAO-A, beta site amyloid precursor protein cleaving enzyme 1 (BACE-1), β-amyloid (Aβ) aggregation, tau phosphorylation, and an ability to cross blood-brain barrier (BBB). With a multitarget approach and minimal side effects, they could revolutionise the treatment of AD. Many phytochemicals and their derivatives are under clinical and pre-clinical trials, potentially serving as prospective therapeutic drug candidates for treating AD. This review briefly discusses the findings and advances in knowledge about plant-derived bioactive compounds as potential new drugs acting as AChE inhibitors.

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Depression is associated with executive cognitive deficits which are not well explored and treated. Such deficits have a significant impact on remission and recurrence. To understand the neurocognitive mechanisms of executive processes, a literature search was conducted using bibliographic databases in neuroscience and cognitive sciences: PubMed, ScienceDirect, EBSCOhost, and PsyArxiv, combining search terms: “depression”, “executive functions”, and “specific brain event-related potentials”. The theoretical review focuses on experiments using electrophysiological techniques, non-invasive tools with high temporal resolution. Depression shows alterations in brain activity linked with cognition: P3 diminished amplitudes and prolonged latencies, indicating executive attentional dysfunction; similar activity characterizes mismatch negativity (MMN), reflecting difficulties for change detection, voluntary effort, and mental shifting. Besides, depression tends to increase N1 latencies related with discrimination, and amplitudes of loudness dependence of auditory evoked potentials (LDAEP), suggesting inhibitory control’s deficits. Regarding feedback processing, the alterations of error-related negativity (ERN), correct response negativity (CRN), and error positivity (Pe), at anterior cingulate cortex (ACC), and frontal regions, are related with troubles for error awareness, cognitive control, and error monitoring in depression. Lastly, the ability to interpret coherently the information value of negative feedback (NF), and a propensity to commit perseverative and non-perseverative errors, need further investigation. Depressive individuals commit both errors on more occasions than controls, what seems to relate with fronto-striatal networks’ alterations, producing visual attention deficits and difficulties for inhibiting incoming information. Results show a variety of brain and executive cognitive components that are impaired under depression, although further research may clarify controversies resulting from depression heterogeneity and methodology used.

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Spinal myelopathies, characterized by neurological deficits due to spinal compression in the spinal column, are increasingly common in the aging population. Although spinal myelopathies commonly present with sensory and motor deficits, they also manifest with life-debilitating enteric dysfunction associated with increased gastroparesis, constipation, bloating, abdominal pain, neurogenic bowel disease, and bladder and bowel incontinence. That said, the effects of spinal myelopathies on enteric gastrointestinal (GI) function are still poorly understood. This review aims to summarize existing literature concerning spinal myelopathies and their effect on the GI system, including the relevant anatomy and physiology of the nervous systems, etiology of various spinal cord injuries, clinical manifestations, current diagnosis and treatment strategies, and ongoing research concerning the gut-brain-spinal axis. The autonomic nervous system contributes to GI innervation through enteric reflex arcs and communication with the central nervous system (CNS) via spinal nerves. When spinal cord damage occurs, enteric reflex arcs, autonomic regulation, and gut-brain-spinal axis can become impaired, leading to GI symptoms. Etiologies of spinal myelopathies occur at all spinal levels. Spinal myelopathy includes inflammatory processes, such as multiple sclerosis and infection, and non-inflammatory processes, such as spondylosis, degenerative disc disease, tumors, and traumatic spinal cord injuries. Diagnosis modalities include imaging, particularly MRI, and functional assessments, such as high-resolution anorectal manometry and colonic transit studies. Enteric dysfunction treatment includes non-pharmacological, pharmacological, neuromodulatory interventions, and surgery. These strategies encompass lifestyle modifications, laxatives, prosecretory agents, 5HT4 agonists, vagus nerve stimulation, sympathetic nerve stimulation, colostomy, and ileostomy. Despite these treatment options, ongoing research with pudendal nerve stimulation, transanal irrigation, mesenchymal stem cells, and the relationship between the gut microbiome and gut-brain-spinal nerve axis may be beneficial in understanding spinal cord myelopathy-related enteric dysfunction, diagnosis, and treatment, ultimately improving clinical outcomes and quality of life for those who are affected.

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Alzheimer’s disease, the main cause of dementia worldwide, is a slowly progressive neurodegenerative disorder. This disease involves a diversity of etiophatogenic processes as it is not only a genetic but also a biological and environmental disease. Owing to that complexity, nowadays there is no efficacious treatment for this disorder. The major Alzheimer’s disease clinical indications include extracellular senile plaques of amyloid-β protein, intracellular hyperphosphorylated τ neurofibrillary tangles, uncommon neuroinflammatory response, oxidative stress, and synaptic and neuronal dysfunction. The evaluation of the neuroprotective potential of new compounds is imperative. As natural products, like phenolic compounds, exhibit several bioactivities, it is urgent to test them and evaluate their inhibition of each clinical indication of Alzheimer’s disease. If phenolic compounds target more than one Alzheimer’s disease pathogenic mechanism (multi-target drug ligands), they will have the potential of becoming a leading Alzheimer’s disease treatment. Thus, this review analyzes, for each Alzheimer’s disease clinical indication, the scaffolds of several phenolic compounds leading to the highest activity with the objective to find phenolic compounds active against all the clinical indications. It was concluded that compounds presenting scaffolds like rugosin E or isocorilagin show potential in combating Alzheimer’s disease.

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All living beings, from microorganisms to plants, animals, and humans, require iron as an essential micronutrient for their lives. However, iron overload can constitute a scenario prone to damage to the organism, including oxidative stress, deterioration of cellular and subcellular membranes, and thus leading to cell death. This process involves unrestricted lipid peroxidation caused by the generation of reactive oxygen species (ROS) because of an abrupt increase in free Fe²⁺ in the cytoplasm, all of which leads to subsequent membrane damage and iron-dependent cell death, now known as “ferroptosis”. This process can be induced by convulsive stress, and conversely, inducing seizures, and in both situations under a context of neuroinflammation. In this critical review, we will highlight the most relevant aspects of this recently described mechanism, which has been studied little in epilepsy, its impact on the prognosis of the disease, and its effects on the development of central and/or peripheral comorbidities, including SUDEP (sudden unexpected death in epilepsy).

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