The presence of insoluble aggregates of amyloid β (Aβ) in the form of neuritic plaques (NPs) is one of the main features that define Alzheimer’s disease. Studies have suggested that the accumulation of these peptides in the brain significantly contributes to extensive neuronal loss. Furthermore, the content and distribution of cholesterol in the membrane have been shown to have an important effect on the production and subsequent accumulation of Aβ peptides in the plasma membrane, contributing to dysfunction and neuronal death. The monomeric forms of these membrane-bound peptides undergo several conformational changes, ranging from oligomeric forms to beta-sheet structures, each presenting different levels of toxicity. Aβ peptides can be internalized by particular receptors and trigger changes from Tau phosphorylation to alterations in cognitive function, through dysfunction of the cholinergic system. The goal of this review is to summarize the current knowledge on the role of lipids in Alzheimer’s disease and their relationship with the basal cholinergic system, as well as potential disease-modifying therapies.

Alzheimer’s disease (AD) represents an escalating global health crisis, constituting the leading cause of dementia among the elderly and profoundly impairing their quality of life. Current FDA-approved drugs, such as rivastigmine, donepezil, galantamine, and memantine, offer only modest symptomatic relief and are frequently associated with significant adverse effects. Faced with this challenge and in line with advances in the understanding of the pathophysiology of this neurodegenerative condition, various innovative therapeutic strategies have been explored. Here, we review novel approaches inspired by advanced knowledge of the underlying pathophysiological mechanisms of the disease. Among the therapeutic alternatives, immunotherapy stands out, employing monoclonal antibodies to specifically target and eliminate toxic proteins implicated in AD. Additionally, the use of medicinal plants is examined, as their synergistic effects among components may confer neuroprotective properties. The modulation of the gut microbiota is also addressed as a peripheral strategy that could influence neuroinflammatory and degenerative processes in the brain. Furthermore, the therapeutic potential of emerging approaches, such as the use of microRNAs to regulate key cellular processes and nanotherapy, which enables precise drug delivery to the central nervous system, is analyzed. Despite promising advances in these strategies, the incidence of Alzheimer’s disease continues to rise. Therefore, it is proposed that achieving effective treatment in the future may require the integration of combined approaches, maximizing the synergistic effects of different therapeutic interventions.

Despite aggressive current therapies against glioblastoma (GB), residual tumor cells may remain at the edge of the surgical cavity after resection. These cells can rapidly proliferate, giving rise to tumor recurrence in more aggressive and drug-resistant forms. As photodynamic therapy (PDT) has advanced, it has emerged as an option to treat this brain tumor. The oncological basis of PDT involves the selective accumulation of a photosensitizer (PS) in the tumor, followed by its activation with electromagnetic radiation to generate reactive oxygen species (ROS), which induce tumor cell death. Given that first- and second-generation PSs present significant limitations, including poor tumor selectivity, suboptimal biodistribution, limited absorption within the therapeutic window, and slow systemic clearance, research has progressed toward the development of third-generation PSs based on nanotechnology to optimize their therapeutic properties. This review addresses the types of tumor cell death induced by PDT, as well as the advancements of PS design, focusing on titanium dioxide (TiO₂) and zinc oxide (ZnO) nanoparticles. These nanomaterials can be designed as carriers, encapsulating or conjugating conventional PSs, or act as PSs themselves, due to their favorable biocompatibility and intrinsic photoreactivity. Additionally, they can be functionalized with targeting ligands to achieve tumor-specific delivery, enhancing therapeutic selectivity while minimizing toxicity to healthy tissue. Overall, these nanotechnology-based PSs represent a versatile and promising therapeutic paradigm that warrants further investigation through basic research, supporting the development and potential clinical translation of a more precise and effective PDT-based intervention for glioblastoma, initially aimed at eliminating intra-surgical post-resection residual tumor cells.

Progesterone (P4) is a neuroactive hormone having pleiotropic effects, supporting its pharmacological potential to treat global (cardiac-arrest-related) cerebral ischemia, a condition associated with an elevated risk of dementia. This review examines the current biochemical, morphological, and functional evidence showing the neuroprotective/neurorestorative effects of P4 against global cerebral ischemia (GCI). Experimental findings show that P4 may counteract pathophysiological mechanisms and/or regulate endogenous mechanisms of plasticity induced by GCI. According to this, P4 treatment consistently improves the performance of cognitive functions, such as learning and memory, impaired by GCI. This functional recovery is related to the significant morphological preservation of brain structures vulnerable to ischemia when the hormone is administered before and/or after a moderate ischemic episode; and with long-term adaptive plastic restoration processes of altered brain morphology when treatment is given after an episode of severe ischemia. The insights presented here may be a guide for future basic research, including the study of P4 administration schemes that focus on promoting its post-ischemia neurorestorative effect. Furthermore, considering that functional recovery is a desired endpoint of pharmacological strategies in the clinic, they could support the study of P4 treatment for decreasing dementia in patients who have suffered an episode of GCI.