Alzheimer's disease (AD) is a progressive neurodegenerative disorder with multifaceted risk factors, including diet and metabolic dysfunction. The rising prevalence of AD and diabetes has drawn attention to their shared pathophysiological mechanisms. The "cafeteria diet," characterized by high-fat, high-sugar, and energy-dense foods, has emerged as a significant contributor to metabolic dysfunctions, including obesity and insulin resistance, which are risk factors for both diabetes and neurodegenerative diseases. This study explores the effects of the cafeteria diet on cognitive impairment, AD pathology, and its potential role in exacerbating diabetes-related neurological complications. Animal models were subjected to cafeteria diets, mimicking human dietary patterns, to investigate changes in brain structure, amyloid-beta accumulation, tau hyperphosphorylation, and cognitive function. Additionally, metabolic profiling demonstrated the development of insulin resistance and other hallmarks of diabetes, which were closely correlated with the severity of cognitive deficits. Neuropathological analyses revealed exacerbated amyloid-beta accumulation and increased neuroinflammation, linking dietary-induced diabetes to AD pathophysiology. These findings underscore the critical role of dietary habits in modulating the risk and progression of AD, highlighting the importance of interventions targeting metabolic health to mitigate cognitive decline. This study emphasizes the need for further research to unravel the molecular mechanisms underlying the diet-diabetes- AD axis and develop targeted therapeutic strategies.

Background: Diabetes mellitus (DM) is an extremely complex metabolic disorder, with many factors contributing to persistent hyperglycaemia, redox dysregulation, and micro- and macrovascular damage over time. There is growing evidence that oxidative stress is one of the main mechanisms of β-cell damage, insulin resistance, and consequent tissue damage, pointing to the need for therapies to modulate metabolic and redox responses. The extensive nature of quinones has revealed that they can be potential dual-acting redox-active compounds that may have antioxidant and antidiabetic activities. Objectives: This review aims to evaluate quinones from a pharmaceutical perspective, considering the chemical diversity and structure–activity relationships, the physicochemical parameters pertinent to drug development, and the mechanisms of action in terms of glucose homeostasis, insulin signalling, mitochondrial protection, and glycoxidative damage. Methods: Narrative review of the evidence from medicinal chemistry, experimental pharmacology, pharmacokinetics, formulation research, and clinical studies of the potential role of quinones in diabetes and its complications. The paper addresses the relationship between chemical structure and biological activity, redox-dependent mechanisms of action, tissue-protective actions, challenges associated with delivery, toxicity, and recent approaches to formulation. Results: Quinones influence several processes implicated in diabetes, including mitochondrial dysfunction, oxidative stress, pancreatic β-cell injury, insulin signalling impairment, AGE-RAGE activation, and chronic inflammation. Currently, CoQ10 has the strongest evidence in humans, while thymoquinone (TQ), pyrroloquinoline quinone (PQQ), anthraquinones, and mitochondria-targeted derivatives have mainly cellular and animal studies to support them. Low solubility, variable systemic exposure, rapid metabolism, and the potential for pro-oxidant effects at high concentrations continue to hamper therapeutic development of these compounds. Conclusions: Future research scopes will rely on rational derivatisation, precision delivery technologies, and clinically validated safety frameworks to translate redox pharmacology into effective therapeutic interventions.

Mitochondria play a central role in synchronizing energy metabolism, calcium signaling, and redox control, which are essential for neuronal survival and cognitive function. Despite the brain’s small size, its high metabolic demands are met through oxidative phosphorylation, which supports synaptic connections and the cycling of neurotransmitters. Mitochondria integrate processes such as glucose utilization and ketone metabolism to enhance neuronal resilience. This chapter discusses recent findings, highlighting the role of mitochondrial calcium in regulating ATP production to meet synaptic demands and the detrimental effects of excessive calcium influx. It also examines the dual role of reactive oxygen and nitrogen species in signaling and oxidative damage. The energetic costs of maintaining neural balance are illustrated through various neurotransmitter systems, and disruptions in these pathways are linked to neurodegenerative diseases like Alzheimer’s and Parkinson’s. New therapeutic approaches, including mitochondrial-targeted antioxidants and dietary interventions, are explored as strategies to restore mitochondrial health, underscoring their significance in neurological disorders.

Alzheimer's and Parkinson's diseases are devastating brain disorders. The complex pathophysiology of the diseases and the lack of effective treatments have left them almost unexplored and untreatable. One potential approach to PD and AD therapy development is through exosomes, a delivery system that can be translated from innovative delivery techniques into clinical use. These exosome-based therapeutics will require thorough testing, research-driven refinement of engineering methods, and collaboration among scientists, clinicians, and industry to develop exosome therapeutics for clinical use. This review explores the biological properties of exosomes, recent engineering advances to improve their therapeutic potential, and new methods to leverage their versatility for selective delivery of remedial agents to the brain. In addition, preclinical evidence demonstrates that exosomes can modulate amyloid-β aggregation, α-synuclein pathology, neuroinflammation, and mitochondrial dysfunction. Yet difficulties related to mass production, maintaining quality, and obtaining regulatory approvals to bring them into clinical practice remain significant limiting factors. The authors point out the therapeutic advantages and drawbacks of exosome-based drug delivery systems. Besides, it provides a roadmap for harnessing these methods effectively as medical interventions for Alzheimer's and Parkinson's disorders, thereby promoting more studies in the area. Finally, we outline a conceptual model for translating novel exosome-based delivery methods into clinically applicable treatment modalities for Alzheimer's and Parkinson's diseases, thereby encouraging continued exploration in this promising field of research.