Neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s, and Amyotrophic Lateral Sclerosis, are characterized by multifactorial pathologies that extend beyond neuronal loss to include neuroinflammation, oxidative stress, mitochondrial dysfunction, and glial dysregulation. Despite extensive research, disease-modifying therapies remain elusive, hindered by late diagnosis, limited availability of specific biomarkers, and the persistent dominance of reductionist, single-target strategies. This comprehensive and informative review provides a critical synthesis of integrated neuroprotective strategies, with particular focus on glial mechanisms and biomarker-guided interventions. Therapeutic emphasis is placed on coordinated mechanisms targeting both neurons and non-neuronal cells, such as astrocytes, microglia, and oligodendrocytes. Emerging strategies are reported to include modulation of synaptic plasticity and neurotransmission, delivery of neurotrophic factors, activation of intrinsic cytoprotective pathways (e.g., Nrf2 signaling), restoration of proteostasis, and induction of regeneration via cellular reprogramming. Glial cells are discussed as therapeutic targets involved in inflammation, metabolism, myelination, and neuronal survival. Advances in predictive, preventive, personalized, and participatory (P4) medicine, supported by genomics, multi-omics, imaging, and real-world data, are presented as accelerating biomarker discovery and enabling earlier and more precise stage-specific interventions. Future success in combating neurodegeneration will depend on integrated approaches that combine protective, supportive, and regenerative strategies, appropriate for disease stage and patient profile. By reframing neuroprotection as a systemic, multicellular endeavor, this review highlights the potential to not only extend life expectancy, but also preserve meaningful quality of life in individuals affected by neurodegenerative diseases.

Polyunsaturated fatty acids (PUFAs) are critical for human health, serving as key components of cellular membranes and regulators of various physiological functions. Since the body can endogenously synthesize only a small amount of these fatty acids from precursors, adequate dietary intake is essential. This article discusses the vital role of omega-3 fatty acids, particularly docosahexaenoic acid (DHA), in fetal brain development, with maternal omega-3 intake during pregnancy linked to improved neurodevelopment and long-term cognitive outcomes. However, variability in study findings highlights the need for further research to clarify DHA’s mechanisms of action. This article explores recent findings indicating that insufficient omega-3 levels during pregnancy disrupt key neurodevelopmental processes, particularly microglial function, potentially elevating the risk of cognitive impairments and neurodevelopmental disorders, highlighting the need for further research to confirm these effects and elucidate underlying mechanisms and long-term consequences. Ensuring adequate maternal omega-3 intake is vital for supporting healthy brain development and reducing these risks. Additionally, DHA and eicosapentaenoic acid (EPA) show promise in treating pediatric depression by modulating the gut-brain axis, reducing neuroinflammation, and restoring autonomic nervous system function—mechanisms implicated in depression. While omega-3 supplementation holds potential as an adjunctive treatment for pediatric major depressive disorder (MDD), further research is necessary to refine dosing strategies and explore underlying mechanisms, ultimately advancing neuropsychiatric care.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting 1% of the population above sixty years. It is caused by an interaction between genetic and environmental risk factors. Loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) is pathologically characterizing the disease and responsible for the cardinal motor symptoms, most notably, bradykinesia, rest tremors, rigidity, and loss of postural reflexes. Non-motor signs such as olfactory deficits, cognitive impairment, sleep behavior disorders, and gastrointestinal disturbances are reflecting disturbances in the non-dopaminergic system. They precede dopaminergic neuronal degenerations by 5–10 years and are considered the main contributors to patients’ disability, particularly after the successful implementation of levodopa (L-dopa) treatment of motor symptoms. The present general review aimed to briefly update non-motor signs and their underlying pathophysiology in PD.