Pamela David

Mitochondria are critical for bioenergetics, calcium and redox homeostasis, and apoptosis in neurons. Neurons are especially susceptible to mitochondrial malfunction since they are terminally differentiated and have extraordinary energy requirements. Mechanisms such as defective oxidative phosphorylation, altered fission-fusion dynamics, defective mitophagy, impaired axonal transport and excessive reactive oxygen species (ROS) generation are increasingly appreciated as important mechanisms in major neurodegenerative diseases (NDDs) like Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD). The review discusses the structure and function of mitochondria with emphasis on oxidative phosphorylation, ROS and reactive nitrogen species (RNS) signalling, calcium-mediated excitotoxicity, lipid metabolism, and apoptotic and non-apoptotic cell-death mechanisms including necroptosis, ferroptosis, pyroptosis and parthanatos. In particular, disease-specific processes are highlighted, such as impaired mitophagy by amyloid β/tau in AD, PTEN-induced kinase 1 (PINK1)/Parkin dysfunction and complex I inhibition in PD, Superoxide Dismutase 1 (SOD1)/C9orf72-associated mitochondrial defects in ALS, and bioenergetic dysfunction by mutant huntingtin in HD. Therapeutic approaches include mitochondria-targeted antioxidants, fusion and biogenesis enhancers, fission inhibitors, inflammasome modulators, Mitochondrial Permeability Transition Pore (mPTP) inhibitors and gene therapy. Also highlighted are recent advancements such as Ubiquitin-Specific Peptidase 30 (USP30) inhibition, intercellular mitochondrial transfer and regulatory approval of a mitochondria-targeted peptide, together with evidence supporting causality and hurdles underpinning clinical translation. Graded against human-genetic, patient-tissue and model-based evidence, mitochondrial dysfunction is best supported as a primary driver in PD and genetic ALS, and as an early amplifier of proteinopathic or mutant-huntingtin toxicity in sporadic AD and HD.

Background: Neuromycoses, fungal infections affecting the central nervous system (CNS), cause approximately 112,000 deaths annually, representing 19% of AIDS-related deaths globally. Conventional antifungal drugs are limited by poor blood-brain barrier (BBB) penetration, systemic toxicity, and increasing drug resistance. Lipid nanoparticles (LNPs) have emerged as promising vehicles for enhancing antifungal efficacy while modulating immune responses. Thus, this comprehensive review synthesizes current knowledge on LNPs as vehicles for antifungal immune modulators, including their design principles, drug delivery mechanisms, physiological interactions, translational potential, and roadmap for next-generation precision medicine approaches to treating neuromycoses. Methods: A comprehensive narrative review of original studies on LNP-based approaches for neuromycoses was conducted. The literature was synthesized using a structured evidence table encompassing six studies published between 2019 and 2026, including one randomized clinical trial in adults, one case report, one in vitro study, two animal studies, and one study incorporating both in vitro and in vivo approaches. Original research studies were prioritized, while reviews, commentaries, and editorials were excluded. Findings: This review shows four principal findings: (1) LNP formulations achieved mean fungicidal activity of 0.402 log₁₀ CFU/mL/day, non-inferior to intravenous amphotericin B, with 18-week survival and reduced toxicity compared to intravenous formulations; (2) LNPs cross the BBB with limited or no systemic toxicity while enabling intracellular trafficking through optimization of lipid composition and surface chemistry; (3) RMT demonstrates high specificity affected by variability in receptor expression, while AMT and TMT operate through distinct mechanisms with their own potential off-target effects; and (4) encapsulation reduces nephrotoxicity and hepatotoxicity compared to free antifungal drugs, with amphotericin B-loaded NLC showing reduced nephrotoxicity in vitro compared to conventional formulations. Conclusion: These findings highlight the potential of LNP-based antifungal delivery and the need for further clinical validation before broader clinical translation.

Neurite outgrowth, also known as neuritogenesis, is among the crucial factors contributing to the overall neuroplasticity and maintenance of a healthy nervous system. The neurite outgrowth activities of two medicinal mushrooms, i.e. Hericium erinaceus and Lignosus rhinocerotis, have been previously demonstrated in multiple in vitro models showcasing their nerve growth factor (NGF)-promoting activities. In this study, the neuritogenic effects of hot aqueous extracts from H. erinaceus (HE) fruiting bodies and the sclerotium of L. rhinocerotis (LR) were investigated in the HT-22 mouse hippocampal neuronal cell line with potential association to the brain-derived neurotrophic factor (BDNF) expression. Findings show that HE and LR up to 400 μg/mL were non-toxic to HT-22 cells, as measured in the MTT viability assay. In neurite outgrowth assays, HEaq at 25 μg/mL significantly (P < 0.05) increased the number of neurite-bearing cells. Meanwhile, LRaq at as low as 6.25 and 12.5 μg/mL remarkably (P < 0.01; P < 0.001) improved the neurite outgrowth activities. Both HEaq and LRaq significantly (P < 0.0001) upregulated the mRNA expressions of BDNF, the neurotrophic factor responsible for hippocampal neuroplasticity. Immunofluorescence studies have further shown the protein expression of BDNF and neurofilament. These findings suggest that the aqueous extracts of HE and LR could play a vital role in enhancing neuroplasticity and maintaining a healthy nervous system, paving the way for their potential application in neurodegenerative disease management and cognitive health.

Purpose: The teaching and learning of anatomy has experienced a significant paradigm shift. The present study assessed the level of knowledge in anatomy in medical postgraduate students and explored the impact of interventions in the form of anatomical videos on knowledge obtained. An awareness of the importance of human anatomy for clinical skills was created to ensure a certain level of competence be achieved by the end of the anatomy course.Design/methodology/approach: Postgraduate medical students were recruited from various specialties on voluntary basis. The first step was to conduct a preliminary screening exam to determine the level of anatomical knowledge. The students were then divided into two groups at random, one of which received no intervention (the control group), and the other of which watched the videos with content that was pertinent to the practical demonstrations (intervention). To assess the effects of the video intervention, a post-test was administered to all students.Findings: Both spot tests (SPOTs) and short answer question (SAQ) components for scores of all the regions from the intervention groups were comparable to the scores obtained by the post-test control group, although the findings were not significant (p > 0.05). However, the intervention group from the abdomen (ABD) region did perform significantly better (p < 0.05) than the screening test score.Originality/value: The results of the research study imply that interventions like anatomical videos can bridge the postgraduate trainee’s anatomy knowledge gap in a practical method which will immensely help in increasing their knowledge.

Obesity may cause behavioral alterations, while maternal obesity can contribute to metabolic disorders in subsequent generations. The effect of β-glucan-rich Pleurotus pulmonarius (βgPp) was investigated on mouse neurobehavior and hippocampus and its offspring's hippocampus development. Female ICR mice were fed with normal diet (ND), ND with βgPp, high-fat diet (HFD), or HFD with βgPp for 3 months followed by behavioral test and mating. Immunohistochemistry for the expression of neuronal nuclear protein (NeuN) and ionized calcium binding adaptor molecule-1 (Iba-1) in the hippocampus was carried out. βgPp significantly enhanced short-term object recognition memory in HFD-fed mice. βgPp also ameliorated the histological alterations and neuronal loss and increased Iba-1-positive microglia in the hippocampus regions of HFD-fed mice and their male offspring. These findings demonstrated that βgPp supplementation attenuated the effects of HFD on object recognition memory and the alterations on the hippocampal regions of maternal mice and their male offspring.

Age-related macular degeneration (AMD) is a multifactorial disease associated with anatomical changes in the inner retina. Despite tremendous advances in clinical care, there is currently no cure for AMD. This review aims to evaluate the published literature on the therapeutic roles of natural antioxidants in AMD. A literature search of PubMed, Web of Science and Google Scholar for peer-reviewed articles published between 1 January 2011 and 31 October 2021 was undertaken. A total of 82 preclinical and 18 clinical studies were eligible for inclusion in this review. We identified active compounds, carotenoids, extracts and polysaccharides, flavonoids, formulations, vitamins and whole foods with potential therapeutic roles in AMD. We evaluated the integral cellular signaling pathways including the activation of antioxidant pathways and angiogenesis pathways orchestrating their mode of action. In conclusion, we examined the therapeutic roles of natural antioxidants in AMD which warrant further study for application in clinical practice. Our current understanding is that natural antioxidants have the potential to improve or halt the progression of AMD, and tailoring therapeutics to the specific disease stages may be the key to preventing irreversible vision loss.

Oxidative stress and inflammation in neuron-glia system are key factors in the pathogenesis of neurodegenerative diseases. As synthetic drugs may cause side effects, natural products have gained recognition for the prevention or management of diseases. In this study, hot water (HE-HWA) and ethanolic (HE-ETH) extracts of the basidiocarps of Hericium erinaceus mushroom were investigated for their neuroprotective and anti-inflammatory activities against hydrogen peroxide (H₂O₂)-induced neurotoxicity in HT22 mouse hippocampal neurons and lipopolysaccharide (LPS)-induced BV2 microglial activation respectively. HE-ETH showed potent neuroprotective activity by significantly (p < 0.0001) increasing the viability of H₂O₂-treated neurons. This was accompanied by significant reduction in reactive oxygen species (ROS) (p < 0.05) and improvement of the antioxidant enzyme catalase (CAT) (p < 0.05) and glutathione (GSH) content (p < 0.01). Besides, HE-ETH significantly improved mitochondrial membrane potential (MMP) (p < 0.05) and ATP production (p < 0.0001) while reducing mitochondrial toxicity (p < 0.001), Bcl-2-associated X (Bax) gene expression (p < 0.05) and nuclear apoptosis (p < 0.0001). However, gene expression of Nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) were unaffected (p > 0.05). HE-ETH also significantly (p < 0.0001) reduced nitric oxide (NO) level in LPS-treated BV2 indicating an anti-inflammatory activity in the microglia. These findings demonstrated HE-ETH maybe a potential neuroprotective and anti-inflammatory agent in neuron-glia environment.

Background: Mushrooms are not only regarded as gourmet cuisine but also as therapeutic agent to promote cognition health. However, little toxicological information is available regarding their safety. Therefore, the aim of this study was to screen selected ethno-pharmacologically important mushrooms for stimulatory effects on neurite outgrowth and to test for any cytotoxicity.Methods: The stimulatory effect of mushrooms on neurite outgrowth was assessed in differentiating mouse neuroblastoma (N2a) cells. Neurite length was measured using Image-Pro Insight processor system. Neuritogenesis activity was further validated by fluorescence immunocytochemical staining of neurofilaments.In vitrocytotoxicity was investigated by using mouse embryonic fibroblast (BALB/3T3) and N2a cells for any embryo- and neuro-toxic effects; respectively.Results: Aqueous extracts ofGanoderma lucidum,Lignosus rhinocerotis,Pleurotus giganteusandGrifola frondosa; as well as an ethanol extract ofCordyceps militarissignificantly (p < 0.05) promoted the neurite outgrowth in N2a cells by 38.4 ± 4.2%, 38.1 ± 2.6%, 33.4 ± 4.6%, 33.7 ± 1.5%, and 35.8 ± 3.4%; respectively. The IC₅₀values obtained from tetrazolium (MTT), neutral red uptake (NRU) and lactate dehydrogenase (LDH) release assays showed no toxic effects following 24 h exposure of N2a and 3T3 cells to mushroom extracts.Conclusion: Our results indicate thatG. lucidum,L. rhinocerotis,P. giganteus,G. frondosaandC. militarismay be developed as safe and healthy dietary supplements for brain and cognitive health.