Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by neuronal loss, cognitive decline, and pathological hallmarks such as amyloid-beta (Aβ) plaques and tau neurofibrillary tangles. Recent evidence highlights autophagy as a pivotal mechanism in cellular homeostasis, mediating the clearance of misfolded proteins and damaged organelles. However, impaired autophagy contributes significantly to AD pathogenesis by disrupting proteostasis, exacerbating neuroinflammation, and promoting synaptic dysfunction. This review aims to scrutinize the intricate relationship between autophagy dysfunction and AD progression, explaining key pathways including macroautophagy, chaperone-mediated autophagy (CMA), and selective autophagy processes such as mitophagy and aggrephagy. This further extends the discussion beyond the central nervous system, evaluating the role of hepatic autophagy in Aβ clearance and systemic metabolic regulation. An understanding of autophagy’s involvement in AD pathology via various mechanisms could give rise to a novel therapeutic strategy targeting autophagic modulation to mitigate disease progression in the future.

Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease, multiple sclerosis, and amyotrophic lateral sclerosis share converging mechanisms of neuronal dysfunction, including protein aggregation, oxidative stress, and chronic neuroinflammation. Glial cells, once considered passive supporters, are now recognized as central drivers of these processes, offering both pathogenic triggers and therapeutic opportunities. Yet, despite compelling preclinical evidence, the translation of glial-targeted therapies into clinical success has been limited. This review provides a critical synthesis of current knowledge by examining therapeutic strategies through the lens of their translational challenges and failures. This narrative review highlights how interspecies variability of glial phenotypes, shifting neuroprotective versus neurotoxic states, limited biomarker stratification, and delivery barriers have constrained trials, such as anti-triggering receptor expressed on myeloid cells 2 (anti-TREM2) antibodies in AD and glial cell line-derived neurotrophic factor (GDNF) in PD. By analyzing these obstacles across major neurodegenerative disorders, this review argue that the next stage of glial medicine requires precision approaches that integrate stage-specific phenotyping, biomarker-guided patient selection, and innovative delivery platforms. Understanding not only what has been tried but why translation has stalled is essential to chart a roadmap for effective, disease-modifying glial therapies in the aging brain.

Nephrotoxicity is a condition caused by toxic effects of medications and poisons resulting in the rapid decline of kidney function. Centella asiatica is a medicinal herb with antioxidative and anti-inflammatory characteristics that is used to treat a variety of ailments. The present study intends to explore the ability of Centella asiatica in preventing AlCl3 and D-Galactose-induced nephrotoxicity in rats. In this study 30 male albino Wistar rats were induced with nephrotoxicity using AlCl3 and D-galactose, and oral administration of Centella asiatica extract (100, 200, and 300mg/kg/day) was administered for 70 days. The kidneys were extracted after treatment and levels of oxidative and antioxidative enzymes, serum creatinine, and serum albumin were measured. The kidney's histopathological changes were studied. Administration of Centella asiatica extract significantly increased serum albumin, superoxide dismutase (SOD), and catalase levels in kidney homogenates while suppressing serum creatinine and malondialdehyde (MDA) levels and attenuating histopathological changes associated with nephrotoxicity. Centella asiatica extract lowered serum creatinine and oxidative stress levels in a drug-induced nephrotoxicity rat model, while simultaneously increasing serum albumin levels, as evidenced by mitigation of histological changes and normalisation of biomarkers of oxidative stress in the kidney.

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/Objectives: Heart failure (HF) and cancers share common molecular and pathophysiological mechanisms. However, the association between HF and the risk of developing cancer remains unclear. This systematic review and meta-analysis evaluates the association between HF and the risk of cancer incidence by pooling data from studies that compared cancer incidence in HF patients with non-HF controls. Additionally, it quantifies pooled hazard ratios (HRs) for site-specific cancers. Methods: A systematic literature search was conducted across four databases until March 2025 (PROSPERO: CRD420251001541). Seven studies involving over 1.6 million participants were included. Three studies provided direct HF versus non-HF comparisons. Pooled HRs and their corresponding 95% confidence intervals (CIs) were calculated utilising random-effects models. Results: The pooled estimate for overall cancer in HF was not significant (HR 1.32; 95% CI: 0.94–1.85; p = 0.11). However, site-specific analyses revealed significantly elevated risks for lung cancer (HR 1.66; 95% CI: 1.27–2.16), urinary tract cancers (HR 1.66; 95% CI: 1.51–1.82), haematological cancers (HR 1.47; 95% CI: 1.12–1.94), and colorectal cancer (HR 1.38; 95% CI: 1.04–1.83). The associations with breast and prostate cancers were not significant. Notably, substantial heterogeneity was observed across most cancer sites (I² = 96–98%), apart from urinary tract cancers (I² = 0%). Conclusions: Although the pooled estimate for overall cancer was not significant, the significant findings for specific cancer sites suggest the need for enhanced cancer surveillance in patients with HF. Future research should focus on standardising definitions of HF, ensuring consistent adjustment for confounders, and stratifying data by HF phenotype.

Individuals with cerebral palsy (CP) are at an increased risk of developing respiratory diseases due to various factors, including motor impairments, postural abnormalities, and comorbidities, such as dysphagia and gastroesophageal reflux disease. This paper reviews evidence-based strategies and recommendations for the prevention and management of respiratory diseases in young adults with CP. It highlights the importance of early screening, vaccination, and infection control, as well as the role of pulmonary rehabilitation and physical therapy in improving respiratory function. Non-invasive ventilation and pharmacological management, including bronchodilators and mucolytics, are critical for individuals with compromised lung function. Multidisciplinary care, postural management, and swallowing therapy are key components of a comprehensive treatment approach. In addition, innovations in telemedicine and caregiver education are emerging as effective tools to enhance respiratory care and prevent complications. While challenges remain in accessibility and training, future directions, such as personalized medicine and rehabilitation technologies, offer promising solutions to further improve the respiratory health of individuals with CP. This review underscores the importance of early intervention, coordinated care, and ongoing support to optimize outcomes for individuals with CP and reduce the burden of respiratory diseases.