Although research supports the benefits of Physical Exercise (PE) in treating adolescent depression, data remain limited regarding the most effective types, durations, and intensities of exercise. Moreover, most of the research conducted has focused on short-term outcomes, leaving a notable gap in understanding the long-term sustainability of these benefits. Evaluate the effectiveness of PE in alleviating depressive symptoms in adolescents diagnosed with major depressive disorder (CRD number: CRD42024585812).

With a prevalence of almost one in eight people, psychiatric disorders are increasing at an alarming rate due to changes in lifestyle, stress, and dietary habits. Current diagnostic and treatment strategies for psychiatric disorders remain suboptimal and ineffective. Nanomedicine offers a transformative solution by overcoming critical barriers such as the blood-brain barrier, poor drug solubility, low bioavailability, and systemic side effects. Various nanocarriers like polymeric nanoparticles, dendrimers, liposomes, solid lipid nanoparticles, and inorganic nanomaterials demonstrate enhanced brain targeting, controlled drug release, improved therapeutic efficacy, and minimize systemic side effects across a range of psychiatric conditions. Nanomedicine applications span various psychiatric conditions, including depression, anxiety, schizophrenia, and autism, offering innovative solutions like intranasal drug delivery and ligand-targeted delivery systems. These systems exhibit promise in bypassing the blood-brain barrier and achieving site-specific drug delivery. This review highlights the increasing burden of psychiatric disorders, the limitations of current treatments, and the promise of nanomedicine in overcoming drug delivery challenges. It emphasizes how nanotechnology can enhance the pharmacokinetics and pharmacodynamics of psychotropic drugs, enable targeted and synergistic therapies, reduce side effects, and ultimately advance more personalized and effective psychiatric care.

Aneurysmal Subarachnoid Hemorrhage (SAH) is a devastating cerebrovascular event with high morbidity and mortality rates, and early brain injury following SAH (EBI-SAH) within 72 h leads to a poor prognosis. Despite advances in our understanding of the pathogenesis of EBI-SAH, effective therapeutic strategies remain elusive. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation and failure of antioxidant defense, has emerged as a key contributor to neuronal damage in EBI-SAH. This review aims to synthesize knowledge regarding the core molecular mechanisms of ferroptosis, focusing on its role in EBI-SAH initiation and regulation, and comprehensively evaluate diverse pharmacological agents that inhibit ferroptosis to mitigate EBISAH. Natural products (e.g., dihydroquercetin and ginsenoside Rd), synthetic ferroptosis inhibitors (e.g., ferrostatin-1 and deferoxamine), nanomedicines, and small molecules (e.g., melatonin and semaglutide) exert neuroprotective effects by targeting ferroptosis pathways, including the glutathione (GSH)-glutathione peroxidase 4 (GPX4) axis, Nrf2 signaling, iron chelation, and lipid peroxidation suppression. The findings of this study underscore the therapeutic potential of ferroptosis inhibition as a novel strategy to ameliorate EBI-SAH and provide a foundation for future translational research.

Neuroinflammation plays a pivotal role in diabetes-associated cognitive dysfunction. Icariin (ICA), a bioactive flavonoid from Epimedium, shows neuroprotective potential, though its mechanism remains unclear.

Motor neuron disorders (MNDs), including ALS, are deadly neurodegenerative conditions that cause progressive motor neuron degeneration. With neuroprotection and the potential for neuron regeneration employing MSCs, ESCs, iPSCs, and NSCs, stem cell treatment presents a viable alternative to current medicines, which only control a limited number of symptoms. Following PRISMA criteria, this narrative review methodically screened 1248 records from the Cochrane, Web of Science, PubMed, and Scopus databases. Following a thorough screening process, 22 studies, including preclinical models and 19 clinical trials, were analysed to assess the therapeutic mechanisms, safety, and efficacy of stem cell therapies for MNDs. Mesenchymal stem cell (MSC) therapy has shown a promising safety profile and possible therapeutic efficacy in ALS, with no substantial transplant-related toxicity noted. ALS functional rating scale-revised (ALSFRS-R) scores and forced vital capacity (FVC) assessments from clinical trials, such as those evaluating autologous bone marrow-derived MSCs, demonstrated stabilisation in ALS development. Studies have also emphasised as to how immunomodulation and neurotrophic factors play a part in MSC-based therapies. Recent data indicate that repeated intrathecal MSC injection could extend the duration of therapeutic advantages. Clinical trials have shown safety and early efficacy signals for motor neurons produced from embryonic stem cells (ESCs), especially using AstroRx®. This suggests that ESCs could be a viable option for regenerative medicine. Nonetheless, issues, like host integration and differentiation optimisation, still exist. Although clinical translation is still in its early stages, induced pluripotent stem cells (iPSCs) and their derivatives provide disease modelling and patient-specific therapeutic applications. Stem cell therapy holds promise for treating MND, with MSCs leading the way in current trials. It is necessary to enhance ESC- and iPSC-based techniques to tackle integration issues. To ensure long-term safety and efficacy, therapies must be developed using standardised protocols, patient stratification, optimised delivery, and large-scale studies.

Ischemic stroke occurs when reduced or blocked blood flow prevents oxygen and nutrients from reaching brain tissue, resulting in neurological deficits. It is a leading cause of disability and death worldwide, with varying degrees of brain injury, from tissue damage to neuronal death and functional impairments. While restoring blood flow is necessary, it can worsen damage through oxidative stress, pro-inflammatory cytokines, apoptosis, blood-brain barrier disruption, cerebral edema, and hemorrhagic transformation. Neuroprotection plays a crucial role in reducing ischemic damage, with therapies targeting antioxidant, anti-inflammatory, and anti-ferroptotic pathways being essential. Current treatments for ischemia remain insufficient, and there is a lack of comprehensive reviews on drug candidates targeting this condition. This review aims to address this gap by evaluating 271 potential drug candidates for cerebral ischemia. It presents an in-depth analysis of compounds with core structures such as triazole, piperazine, pyrrole, amide, pyridine, and oxadiazole, along with functional groups like hydroxyl, halogen, and alkyl groups. These compounds exhibit promising neuroprotective, antioxidant, anti-ferroptotic, and anti-inflammatory effects. The encouraging findings highlight the need for further research and optimization to develop more effective therapeutic agents, reduce mortality, and prevent permanent disabilities associated with ischemic brain injuries.

Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder marked by the degeneration of dopaminergic neurons in the substantia nigra, leading to characteristic motor symptoms such as bradykinesia, tremor, and rigidity, as well as a range of non-motor manifestations including cognitive impairment, mood disturbances and autonomic dysfunction. Among the multiple cellular mechanisms implicated in PD, the dysregulation of autophagy has gained significant attention in recent years. Autophagy is a crucial intracellular degradation pathway responsible for the removal of misfolded proteins and damaged organelles, processes that are particularly relevant in neurodegenerative diseases. Impairment of autophagic flux contributes to the accumulation of toxic protein aggregates and cellular stress in PD. Rapamycin, a compound originally isolated from Streptomyces hygroscopicus, is a well-established inhibitor of the mechanistic target of rapamycin (mTOR), a central regulator of autophagy. Preclinical studies have shown that rapamycin can stimulate autophagic pathways by suppressing mTOR signalling, leading to increased expression of autophagy markers. These effects have been associated with reduced neuronal damage, improved motor performance and decreased accumulation of pathological proteins in PD models. This review provides an overview of current preclinical research on rapamycin's neuroprotective potential in PD through autophagy enhancement. Although findings are promising, translating these outcomes into clinical practice necessitates a thorough understanding of rapamycin's pharmacodynamics, optimal dosing strategies, potential side effects and long-term safety. Further research is essential to establish its therapeutic viability in human populations.

Alzheimer's disease (AD) is the primary cause of dementia and a significant threat to healthy aging. The prevalence of AD and other non-communicable diseases (NCDs) is significantly influenced by the progressive decline in physiological functions that is associated with aging.

Neurodegenerative and neurodevelopmental disorders represent a significant global health burden, characterized by progressive neuronal dysfunction and loss. Both diseases, despite their diverse etiologies and mechanisms, share a complex interplay of genetic, environmental, and biological factors. Neurodegenerative diseases are caused by multiple factors, including aging, mitochondrial dysfunction, oxidative stress, inflammation, genetic mutations, and protein misfolding. In contrast, neurodevelopmental disorders are primarily influenced by epigenetic alterations, neurotransmitter imbalances, early brain damage, environmental factors, and genetic variations. Despite extensive research, effective treatments remain unavailable due to the complexity of their pathologies and the biochemical pathways involved. A deep understanding of the complexities and individual differences associated with these disorders is crucial for developing effective treatments. In this background, this review provides a comprehensive overview of neurodegenerative and neurodevelopmental disorders, including their clinical symptoms, etiology, pathogenesis, underlying mechanisms, potential drug targets, reported drugs, advanced treatment options, and challenges in the drug discovery process. This comprehensive literature review was conducted using databases such as PubMed and Scopus, focusing on research published up to April 2025. By understanding the complexities of these disorders, researchers can develop novel therapeutic approaches, including potential drugs and advanced treatment methods, to mitigate their devastating impact.

Autophagy is a catabolic process that helps maintain cellular homeostasis by degrading damaged proteins and organelles while recycling essential biomolecules. Neuropsychiatric disorders, such as schizophrenia, bipolar disorder, major depressive disorder, and substance use disorders, have been linked to autophagy dysregulation. In this manuscript, we review the complex role of autophagy in the neurobiology of these disorders, encompassing neuronal function, neurodevelopment, and neuroplasticity. The molecular mechanisms by which autophagy dysregulation contributes to the manifestation and progression of neuropsychiatric diseases, including those related to autophagy genes and pathways, are also discussed. Additionally, potential entry points for autophagytargeted therapy in these disorders, such as modulating mTOR and combining autophagy modulators with existing treatments, are also explored. We also specifically examine the neuroprotective effects of lithium, a mood stabilizer, through its influence on autophagy pathways. Overall, understanding the intricate relationship between autophagy and neuropsychiatric disorders provides new avenues for developing new treatments for these devastating conditions.

Alzheimer's disease (AD) lacks effective biomarkers and diseasemodifying therapies. This study explored transcriptomic dysregulation, immune-metabolic crosstalk, and drug repurposing opportunities in AD.

Neurological disorders are complex conditions characterized by impairment of the nervous system, affecting motor, cognitive, and sensory functions. Current treatments meet substantial obstacles, primarily due to the difficulty of transporting drugs across the blood-brain barrier and ineffective therapy for nerve regeneration. Emerging technologies, such as electrospinning, offer innovative solutions to overcome these challenges. The study explores the potential of electrospun food fibers in managing and treating neurological disorders, concentrating on their role in drug delivery and nerve tissue regeneration. Electrospinning allows for the generation of nanofibers from diverse natural and synthetic polymers that imitate the extracellular matrix and stimulate brain healing. These fibers may be loaded with therapeutic drugs, permitting controlled, localized drug release while limiting systemic toxicity. For instance, electrospun fibers loaded with neuroprotective drugs, such as donepezil and levodopa, have exhibited better drug stability, enhanced bioavailability, and prolonged therapeutic efficacy in treating syndromes such as Alzheimer's and Parkinson's diseases. Furthermore, the biodegradable and biocompatible nature of food-based polymers like chitosan, cellulose, and zein makes them great candidates for medicinal applications, minimizing the risk of inflammation and unfavorable immunological reactions. In conclusion, electrospun food fibers show tremendous promise in resolving the issues of drug delivery and nerve regeneration in neurological illnesses. Their capacity to boost therapeutic results via targeted and regulated drug release makes them a possible alternative to established treatment procedures, bringing renewed hope to patients suffering from neurodegenerative disorders.

Migraine is a common and debilitating neurological condition marked by recurring headaches and sensory disturbances. Although it poses a significant global health burden, its long-term management remains a challenge. Advances in pathophysiological insights have facilitated the development of more targeted treatment approaches. This review explores current and emerging strategies, including diagnostic methods, risk factors, and both pharmacological and nonpharmacological interventions.

The mobility of people with multiple sclerosis (pwMS) is significantly limited due to the involvement of the musculoskeletal system, resulting in falls and a diminished quality of life. This study aimed to assess the risk of falls (utilizing the Downton scale) and its association with spasticity and other variables in pwMS and compare it with a group of healthy participants.

CNS diseases have recently received a lot of focus. Glioblastoma multiforme (GBM) has the worst prognosis among various cancers. With its aggressive nature and potential for recurrence, GBM is a major concern in neuroscience. Radiotherapy, chemotherapy, and surgical removal are currently employed methods for treating GBM. The blood-brain barrier (BBB) is a major obstacle to effective medication delivery into the central nervous system (CNS), which is a major concern in the treatment of GBM. Nanotechnology helps transport active chemicals to brain tissue, a major glioma treatment challenge. Technology advancements in nanotechnology have the potential to facilitate the trans-BBB delivery of medicinal medications to the central nervous system. To treat illnesses associated with the central nervous system (CNS), it is possible to manage several types of nanoparticles (Nps). Novel therapeutic approaches are being explored, with NPs attracting interest as a potential tool for the targeted eradication of brain tumours. The review article reviewed the relevant literature on the utilisation of NPs for the treatment of Glioblastoma. The articles were obtained through various databases, including ScienceDirect, Scopus, PubMed and Google Scholar. It studies current treatment strategies for Glioblastoma, different NPs treating GBM with their mechanism by crossing the BBB, and various relevant patents of NPs drug delivery were analysed. This review article collects data about various nanoparticles used in GBM, with their mechanism of action. This review discusses the role of nanoparticulate systems in the effective treatment of GBM. It can be concluded from the literature that therapeutic agents can be delivered into the central nervous system through the blood-brain barrier with the use of nanotechnology, and so can be effectively used for the management of GBM.

Although motor neuron inclusions that contain hyperphosphorylated TDP- 43 protein (p-TDP-43) are considered an important clue in the pathophysiology of ALS, the main determinants of the neuronal dysfunction remain unknown.

JNK3 is a specific isoform of c-Jun N-terminal kinase, mainly found in the brain, and is highly sensitive to stress-associated signals in the central nervous system. It has been reported that JNK3 plays a crucial role in neurite formation and cognition. During pathological states such as Alzheimer's disease, cerebral ischemia, Traumatic brain injury (TBI), Parkinson's disease, and epilepsy, it is found to be in a hyperactivated form. Hyperphosphorylation of amyloid precursor protein (APP) and tau leads to toxic Aβ42 and neurofibrillary tangles. Excess Aβ activates JNK3 signaling, causing neuronal loss. JNK3 also contributes to mitochondrial dysfunction, Oxidative stress, neuroinflammation, and apoptosis, driving AD progression.

This systematic review aimed to provide an updated overview of studies using anticholinesterases with in vivo activity for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a leading source of dementia, evidenced by cognitive debility, tau neurofibrillary tangles, and amyloid-β plaques. Recent studies emphasize the gut-brain axis as a vital element in the pathogenesis of Alzheimer's disease, involving microbial, neuronal, immunological, and hormonal mechanisms. The composition of gut microbiota dysbiosis is determined by growth in intestinal barrier permeability and activation of immune cells, which causes impaired function of the blood-brain barrier that stimulates neural injury, neuronal loss, neuroinflammation, and eventually AD. Various studies have reported that the gut microbiota plays a crucial role in brain function and changes in individual behavior, as well as in bacterial amyloid formation. Growing experimental and clinical data specify the conspicuous role of intestinal dysbiosis and microbiota- host interactions in AD. The importance of this paper is the focus on the potential association of AD and gut microbiota and also a discussion of the therapeutic modalities of inhibiting gut dysbiosis.