Physical activity highly impacts the neuroendocrine system and hormonal secretion. Numerous variables, both those related to the individual, including genetics, age, sex, biological rhythms, nutritional status, level of training, intake of drugs or supplements, and previous or current pathologies, and those related to the physical activity in terms of type, intensity, and duration of exercise, or environmental conditions can shape the hormonal response to physical exercise. The aim of this review is to provide an overview of the effects of physical exercise on hormonal levels in the human body, focusing on changes in concentrations of hormones such as cortisol, testosterone, and insulin in response to different types and intensities of physical activity. Regular monitoring of hormonal responses in athletes could be a potential tool to design individual training programs and prevent overtraining syndrome.

Neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, and Huntington’s disease, represent unmet medical and social needs. Still, no definitive cure exists for these illnesses, hence a therapeutic approach with molecules able to prevent/downtone/modify the disease seems highly attractive. Remarkably, a higher risk of neurodegenerative disease is associated with low vitamin D levels. Vitamin D is a multifaceted molecule able to target critical neuroinflammatory processes underlying neurodegeneration, acting through genomic or rapid signaling. This narrative review aims to focus on vitamin D’s potential to be an optimal neuroprotective molecule, based on its ability to target and counteract aberrant biomolecular processes involved in neuroinflammation/neurodegeneration. Noticeably, exercise can potentiate vitamin D’s protective effect through some anti-inflammatory actions exerted on shared biomolecular targets. Thus, although vitamin D is not strictly a drug, it could be potentially allocated within the therapeutic approach to neurodegenerative diseases in combination with adapted exercise, best as an early intervention. Topics on the complexity concerning the doses for supplementation and data discrepancy from trials are addressed. The urgent demand is to test and clarify vitamin D efficacy and safety, combined or not with exercise, in clinical settings.

Neurodegenerative diseases are distinguished by synaptic dysfunction and chronic neuroinflammation, which accelerate neuronal loss and impair network resilience. Synaptic plasticity, that is, the ability to adapt to changes, is progressively lost. This ability is part of hormesis, an adaptive biphasic response, nowadays acknowledged as a promising tool in chronic degenerative diseases, since it offers a framework for personalized interventions. Growing evidence supports exercise as a powerful approach for managing neurodegenerative disorders, due to its capacity to enhance neuroplasticity through the direct targeting of the biomolecular processes involved. Indeed, regular exercise can drive many molecular mediators and signals toward neuroplasticity improvement, potentially slowing neurodegeneration. This narrative review focuses on exercise as a promising therapeutic approach in neurodegenerative diseases, based on its ability to shape synaptic plasticity at the molecular level. Some biomediators involved in synaptic plasticity function/dysfunction and neuroinflammation/neurodegeneration are addressed as therapeutic targets of exercise, and different exercise regimens are discussed as specific therapeutic interventions to contain the burden of some neurodegenerative conditions. Some clinical trials including exercise in the treatment of neurodegenerative diseases are summarized. Since no definitive disease-modifying cure exists for these illnesses, exercise’s ability to shape synaptic plasticity emerges as a highly attractive therapeutic approach.

The chemokine CXCL10 contributes to early autoimmune rheumatic disease (ARD) development. Preclinical ARD stages exhibit dendritic cells (DCs), CD4⁺ T cells, and monocytes (CD14⁺ cells) dysregulation and an overreactive immunoprofile. The peroxisome proliferator-activated receptor (PPAR)β/δ acts as a “molecular brake”, limiting autoimmune overresponse. This study aims to investigate CXCL10 in human monocyte-derived mDCs, CD4⁺ T cells, and monocytes exposed to PPARβ/δ agonist carbaprostacylin (cPGI₂) or PPARγ agonist rosiglitazone (RGZ), to verify drug-class-related effects. Tumor necrosis factor (TNF)α, interferon (IFN)γ, synergistic inducers of CXCL10, and interleukin (IL)-10 were investigated. mDCs, CD4⁺ T cells, and CD14⁺ monocytes isolated from healthy donors’ blood were cultured, specifically activated to mimic an overreactive phenotype, and treated for 24–48 h with/without [10 μM] cPGI₂ or [5 μM] RGZ (near therapy doses, respectively). Luminex assays quantified cell supernatant analytes; Real-time q-PCR measured cytokine and PPARβ/δ mRNA expression. cPGI₂, not RGZ, significantly decreased CXCL10 in mDCs and CD4⁺ T cells, reduced TNFα in mDCs, CD4⁺ T and monocytes, and diminished IFNγ in mDCs. IL-10 did not change. cPGI₂-induced CXCL10 downregulation, with TNFα and IFNγ decrease, might be relevant, given its early activity in ARD development. Scenarios on PPARβ/δ agonist re-positioning aimed at modulating CXCL10 might open opportunities to support ARD management and targeted therapy development.