Sathyabama Institute of Science and Technology (SIST), formerly Sathyabama University, is a deemed to be university, situated at Chennai, Tamil Nadu, India. It was founded in 1987 as Sathyabama Engineering College by the late Jeppiaar and received its deemed to be university status in 2001.
Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, remain leading causes of disability and premature death. Although they present with distinct clinical phenotypes, they converge on several pathogenic processes. Among these, mitochondrial dysfunction has emerged as a key driver of neurodegeneration, encompassing impaired bioenergetic capacity, disturbed calcium handling, altered mitochondrial dynamics, insufficient mitophagy, and excessive production of reactive oxygen species (ROS). This review provides a focused synthesis of the ways in which mitochondrial pathology contributes to neurodegeneration across major neurodegenerative disorders and summarizes therapeutic strategies designed to target mitochondria. We outline disease-relevant mitochondrial abnormalities and connect them to neuronal loss, synaptic failure, and neuroinflammatory cascades, with particular attention to mitochondrial ROS and inflammatory signaling linked to mitochondrial DNA. The manuscript further evaluates current and emerging interventions, including mitochondria-targeted antioxidants, mitochondrial transfer/transplantation, exercise, dietary approaches, and nanotechnology-enabled delivery systems. For each strategy, we consider the mechanistic rationale, key preclinical findings, and barriers to translation. Across experimental models, many of these approaches confer measurable neuroprotection—often reflected by lower oxidative burden, stabilization of mitochondrial membrane potential, and partial restoration of ATP production. However, clinical findings have been inconsistent, suggesting that efficacy depends strongly on disease stage, patient heterogeneity, and the specific mitochondrial defect being targeted. By integrating mechanistic insights with therapeutic evidence, this review offers a structured perspective on shared and disease-specific features of mitochondrial dysfunction and highlights priorities for advancing mitochondria-centered interventions toward meaningful clinical benefit.
Alzheimer's disease (AD) is a devastating neurodegenerative disorder defined by progressive memory loss and synaptic failure. For decades, therapeutic development has focused on clearing amyloid-beta plaques, yet the repeated clinical failures of this approach necessitate a fundamental paradigm shift toward the brain's immunometabolic landscape. The "Viral Mimicry" hypothesis posits that AD represents a state of sterile autoimmunity where the innate immune system mistakenly identifies self-nucleic acids as viral pathogens. This "ghost war" is ignited by the convergence of metabolic dysfunction and genomic instability: specifically, the leakage of mitochondrial DNA into the cytosol and the epigenetic derepression of ancient retrotransposons (LINE-1, HERVs). These endogenous ligands activate the cGAS-STING cytosolic sensing axis, a pathway that drives a chronic interferon response. Consequently, microglia and astrocytes are transformed into senescent, pro-inflammatory phenotypes that release a toxic Senescence-Associated Secretory Phenotype (SASP), directly fueling synaptic elimination. Crucially, major genetic risk factors, including APOE4 and TREM2 variants, exacerbate this cascade by compromising mitochondrial integrity and lipid metabolism, thereby sensitizing the brain to innate surveillance failure. By reconceptualizing AD as an acquired interferopathy driven by the "enemy within," this framework highlights novel therapeutic targets. Specifically, repurposing Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to block retrotransposition and deploying senolytics to clear dysfunctional glia offer promising strategies to arrest the progression from healthy aging to cognitive decline. This review synthesizes current research on the molecular mechanisms of viral mimicry, detailing the impact of genetic risk factors and evaluating emerging therapeutic interventions targeting this innate immune axis.
Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants with high persistence and significant toxic effects on ecosystems and human health. Despite numerous regional studies, a comprehensive understanding of their global distribution across major environmental compartments—soil, water, air, and sediment—is still lacking. This systematic review and meta-analysis address this gap by synthesizing worldwide data to reveal spatial patterns and identify regions with higher contamination levels. Comprehensive searches of PubMed, Scopus, Web of Science, and grey literature identified 15,084 records, of which 79 studies met the inclusion criteria. Random-effects meta-analysis was conducted to estimate pooled PAH concentrations across environmental media and evaluate heterogeneity, sensitivity, and publication bias. The results revealed marked regional disparities, with the highest levels generally reported in Nigeria, Iran, China, and Egypt. Water and soil were the most frequently investigated media (28.7
Hemolysins are a varied group of bacterial toxins that play a significant role in making microbes more harmful by disrupting host cell membranes and affecting host-pathogen interactions. Both Gram-positive and Gram-negative bacteria produce hemolysins, which help them acquire nutrients, avoid the immune system, damage tissue, and spread. This review offers a detailed look at bacterial hemolysins, emphasizing their classification, structural differences, and how they work at a molecular level. It discusses the role of hemolysins in how microbes' function and cause disease, as well as their interactions with host cell responses. The review summarizes current methods for detecting and characterizing hemolysins, highlighting progress in both analytical and molecular techniques. Furthermore, it examines recent advancements in targeting hemolysins through strategies that reduce their harmful effects and therapeutic inhibition. By connecting mechanisms with new intervention strategies, this review stresses the significance of hemolysins in microbial biology and their potential as targets for new antimicrobial methods.
Neuroinflammation and oxidative stress are central mechanisms driving neurodegenerative diseases, while impaired neurogenesis limits regeneration. Aromatic-turmerone (ar-turmerone), a bioactive sesquiterpenoid from Curcuma longa, has emerged as a multifunctional neuroprotective agent capable of modulating inflammatory and regenerative processes simultaneously. Evidence from in vitro and in vivo models demonstrates that ar-turmerone suppresses Toll-like receptor 4 (TLR4)-dependent NF-κB and MAPK signaling, thereby reducing microglial activation, nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory cytokines (TNF-α, IL-1β, IL-6). Concurrently, it activates the Nrf2/HO-1 antioxidant pathway and enhances cAMP/PKA-CREB signaling, restoring redox homeostasis and promoting neuronal survival. Importantly, ar-turmerone drives microglial polarization toward the M2 anti-inflammatory phenotype and stimulates neural stem cell (NSC) proliferation and neuronal differentiation in the subventricular zone and hippocampus. These dual anti-inflammatory and neurogenic actions position ar-turmerone as a unique bridge between neuroinflammation suppression and neuroregeneration enhancement. Recent structure–activity relationship studies further reveal that N-substituted amide and naphthyl derivatives exhibit superior inhibition of NO and TNF-α release and improved neuroprotective potency in Alzheimer’s and Parkinson’s disease models. Collectively, ar-turmerone represents a promising multi-target natural scaffold for developing therapeutics that counteract neurodegeneration by simultaneously modulating microglial activation, oxidative stress, and endogenous neurogenesis.
