Progress In Brain Research[JOURNAL]
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200 papers
AI and emerging technologies for diagnosis.
Soundararajan S, Selvakumar J, Selvakumar V … +1 more , Baskaran N
Prog Brain Res · 2025 · PMID 41314747 · Publisher ↗
Healthcare is undergoing a transformation owing to artificial intelligence in medical diagnostics, which is providing unprecedented levels of efficiency and precision. AI is revolutionizing the detection, analysis, and t...
Healthcare is undergoing a transformation owing to artificial intelligence in medical diagnostics, which is providing unprecedented levels of efficiency and precision. AI is revolutionizing the detection, analysis, and treatment of diseases, especially in the field of medical diagnostics. AI can process enormous volumes of data quickly and effectively by utilizing machine learning and deep learning algorithms, giving healthcare professionals important insights. In addition to improving diagnosis accuracy, these developments are opening the door to early identification and individualized treatment regimens. AI transforms the interpretation of MRIs, computed tomography scans, and X-rays with extreme precision, outperforming humans in the identification of cancerous and vision-related ailments. Early disease identification has been greatly enhanced by the application of AI to identify anomalies associated with neurological and cardiac disorders. By facilitating the rapid identification of cardiac conditions and cancer, predictive analytics helps to significantly lower the number of false positives and negatives. AI reduces errors and human exhaustion and bias, resulting in more equitable and reliable provision of healthcare. With an emphasis on its uses, advantages, and the difficulties associated with incorporating these state-of-the-art technologies into clinical practice, this chapter examines the different ways artificial intelligence is changing medical diagnostics.
Multi-omics integration in disease research.
Ceballos MWG, Sy FFA, Akbar A … +1 more , Taofiq A
Prog Brain Res · 2025 · PMID 41314746 · Publisher ↗
Neurodegenerative diseases, marked by complex molecular mechanisms and diverse clinical features, challenge conventional research approaches. This chapter emphasizes the value of multi-omics integration in understanding...
Neurodegenerative diseases, marked by complex molecular mechanisms and diverse clinical features, challenge conventional research approaches. This chapter emphasizes the value of multi-omics integration in understanding the biology of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Genomic studies reveal risk variants such as APOE ε4 in Alzheimer's and rare mutations in familial forms. Transcriptomics highlights gene expression changes, including synaptic dysfunction in early Parkinson's and alternative splicing errors in TARDBP-related ALS. Proteomics identifies key protein aggregates like amyloid beta and alpha-synuclein, along with modifications such as hyperphosphorylated tau that correlate with cognitive decline. Metabolomics uncovers metabolic alterations, including mitochondrial dysfunction in Parkinson's and lipid peroxidation in ALS, which contribute to disease progression. By combining these layers with high-throughput tools like single-cell sequencing, spatial transcriptomics, and mass spectrometry, researchers can reconstruct molecular networks linking genetic risk, gene regulation, protein dysfunction, and metabolic imbalance. This approach enables patient stratification into molecular subtypes, such as neuroinflammatory clusters defined by microglial gene signatures and cytokine expression. Biomarkers from blood and cerebrospinal fluid allow for minimally invasive disease monitoring. Despite challenges such as data heterogeneity and limited standardization, multi-omics approaches support biomarker discovery and therapeutic development. Integrating these datasets with neuroimaging and digital tools enhances diagnostic precision and guides targeted interventions, such as antisense therapies for SOD1-linked ALS. Multi-omics integration is thus a critical foundation for advancing personalized strategies in neurodegenerative disease research.
Biomarkers: From early detection to treatment personalization.
Fatima S, Tiwari S, Siddiqi B … +2 more , Quadri SN, Abdin MZ
Prog Brain Res · 2025 · PMID 41314745 · Publisher ↗
Neurodegenerative disorders (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), present increasing issues associated with the unavoidable aging of the world's popul...
Neurodegenerative disorders (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), present increasing issues associated with the unavoidable aging of the world's population. These challenges are further highlighted by the socioeconomic consequences of these diseases. The identification and use of biomarkers for prompt diagnosis, careful observation, and efficient treatment approaches is essential to overcoming these obstacles. The primary methods for diagnosing neurodegenerative illnesses are invasive procedures like lumbar punctures to measure CSF fluid or functional brain imaging methods. Biomarkers for underlying proteinopathy in blood serum and cerebral fluid have been the focus of recent biological research, particularly in vivo. With their ability to provide novel pathways for early detection, illness progression tracking, and individualized treatment plans, biomarkers have become essential instruments in precision medicine. The classification of biomarkers including fluid, digital imaging, and molecular biomarkers is examined in this chapter, with an emphasis on their function in neurodegenerative diseases. In neurodegenerative illnesses and the aging brain, tau, amyloid-β, α-synuclein, and TDP-43 are commonly seen to be deposited together rather than separately. These may be disregarded, and it might be challenging to determine their clinicopathological significance. An overview of illness pathophysiology, diagnostic implications, and the most recent molecular and ultrastructural categories for neurodegenerative disorders are given in this chapter. Addressing these issues through interdisciplinary research and technological advancements will be crucial for the future of biomarker-driven precision medicine. This chapter provides an in-depth overview of the evolving landscape of biomarkers and their transformative impact on the early detection and personalized treatment of neurodegenerative diseases.
Precision medicine in neurodegenerative diseases: From research to clinical practice.
Gunasekaran B, Arifin AH, Yu WH … +3 more , Hanafi S, Rao KDK, Salvamani S
Prog Brain Res · 2025 · PMID 41314744 · Publisher ↗
The chapter outlines how precision medicine is reshaping the way neurodegenerative diseases (NDs) which includes Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's d...
The chapter outlines how precision medicine is reshaping the way neurodegenerative diseases (NDs) which includes Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) are understood, diagnosed, and treated. It discusses the limitations of current therapies, which mainly address symptoms without altering disease progression. Genetic and molecular factors that influence disease development are described, including distinctions between familial and sporadic forms. The chapter also covers the roles of epigenetic changes, gene expression, protein dysfunction, mitochondrial DNA, and non-coding RNAs in NDs. Biomarkers in blood and cerebrospinal fluid, along with imaging techniques and digital tools, are presented as key elements in early diagnosis and disease monitoring. Patient stratification based on clinical features, molecular profiles, and biomarkers helps guide treatment decisions and improve outcomes. The chapter reviews ongoing developments in genotype-based drug design, gene therapy, pharmacogenomics, and personalized lifestyle strategies. Clinical case studies show how these approaches are being used in practice. The chapter also discusses challenges in applying precision medicine, such as trial design, data integration, unequal access, and regulatory hurdles. Finally, it highlights the future tools like single-cell transcriptomics, digital twins, and global research collaborations that aim to bring precision approaches into everyday care.
The emergence of the National Articulation of Marijuana Marches (ANMM) in Brazil: A social movement in the context of the COVID-19 pandemic.
Castro D
Prog Brain Res · 2025 · PMID 40967686 · Publisher ↗
His chapter explores the emergence and strengthening of the Articulação Nacional de Marchas da Maconha (ANMM)-the National Articulation of Marijuana Marches-in Brazil during the COVID-19 pandemic. The ANMM, a network of...
His chapter explores the emergence and strengthening of the Articulação Nacional de Marchas da Maconha (ANMM)-the National Articulation of Marijuana Marches-in Brazil during the COVID-19 pandemic. The ANMM, a network of activists and collectives advocating for the legalization of marijuana and the reform of drug policies, represents a significant shift in the anti-prohibitionist movement in Brazil. The pandemic, which forced social movements to adapt to virtual spaces, accelerated the integration of digital technologies into activism, reshaping the strategies and organizational dynamics of the ANMM. Using Bruno Latour's Sociology of Associations (2012), this chapter analyzes the complex interplay between human and non-human actors-such as the internet, social media platforms, and the pandemic itself-in the formation and evolution of the ANMM. The chapter argues that the pandemic not only transformed the way social movements operate but also provided a unique opportunity for the ANMM to consolidate its national presence and amplify its advocacy efforts.
Contributions of the endocannabinoid system to the neurobiology of emotions: Advances and perspectives.
Pontes LR, Ribeiro S
Prog Brain Res · 2025 · PMID 40967685 · Publisher ↗
The endocannabinoid system (ECS) has emerged as a central and multifaceted modulator of emotional physiology, playing a pivotal role in neurotransmission, neuroplasticity, and stress response regulation. This article pro...
The endocannabinoid system (ECS) has emerged as a central and multifaceted modulator of emotional physiology, playing a pivotal role in neurotransmission, neuroplasticity, and stress response regulation. This article provides an original and comprehensive review of the neurobiological mechanisms by which the ECS influences emotional activity, highlighting not only its involvement in psychiatric disorders such as depression, anxiety, and post-traumatic stress disorder, but also offering new perspectives on ECS dysregulation as a common pathophysiological factor in these conditions. The originality of this work lies in its critical integration of recent evidence regarding alterations in receptors, enzymes, and endocannabinoid levels, as well as in its analysis of emerging therapeutic approaches targeting ECS pharmacological modulation, including enzyme inhibitors, selective agonists, and phytocannabinoids. The article emphasizes advances in personalized medicine and the identification of predictive biomarkers for therapeutic response, while also discussing ongoing regulatory and clinical challenges. By critically synthesizing available data, this review makes an innovative contribution to the field, consolidating the ECS as a promising and strategic target for the development of new interventions in mental health.
Green light to sleep: Does cannabis work for insomnia? A case report and brief review.
Mota-Rolim S, Melo PDC, Barroso VV … +3 more , Amaral EJFD, Araujo JF, Ribeiro S
Prog Brain Res · 2025 · PMID 40967684 · Publisher ↗
Insomnia is characterized by difficulty initiating or maintaining sleep and affects 10-20 % of adults. Conventional pharmacotherapies for insomnia, initially comprising benzodiazepines and later the Z-drugs, often presen...
Insomnia is characterized by difficulty initiating or maintaining sleep and affects 10-20 % of adults. Conventional pharmacotherapies for insomnia, initially comprising benzodiazepines and later the Z-drugs, often present significant adverse effects, including dependence and tolerance. Here we provide a brief review on cannabis therapy for insomnia and present a relevant case report. We first discuss the sleep stages and the main clinical aspects of insomnia. Next, we report the case of a 37 year-old patient who, after a grief situation, began to experience insomnia that was resistant to various conventional treatments, even with dosage adjustment. The insomnia diminished after replacing the conventional pharmacotherapies with full spectrum Cannabis sativa oil, rich in cannabidiol (CBD) and tetrahydrocannabinol (THC). Finally, we note that medical societies from several major countries such as England, Australia and Brazil already recommend the use of Cannabis (plants rich in THC and/or CBD) to treat insomnia. These societies base their guidelines on studies that reported a mitigation of the symptoms of insomnia with the use of cannabinoids. However, recent meta-analyses highlight the heterogeneity of the participants, interventions, and results. Further research is essential to elucidate the influence of cannabinoids on both physiological and pathological aspects of sleep.
Cannabinoid treatment impacts adaptive behavior in autism patients and caregivers' mental health: A prospective real-life cohort study.
Guimarães KÁ, Jorge LP, Resende ALO … +4 more , da Silva Junior EA, Kummer AME, da Silva Lessa Júnior W, de Oliveira GNM
Prog Brain Res · 2025 · PMID 40967683 · Publisher ↗
INTRODUCTION: Pharmacological interventions for behavioral symptoms of Autism Spectrum Disorder (ASD) are limited and recent studies point out benefits with the use of cannabinoids. METHOD: This longitudinal observationa...
INTRODUCTION: Pharmacological interventions for behavioral symptoms of Autism Spectrum Disorder (ASD) are limited and recent studies point out benefits with the use of cannabinoids. METHOD: This longitudinal observational study investigates ASD symptoms after 3 months of starting cannabidiol (CBD)-rich extract therapy and it's impact on the mental health of caregivers. Assessment was based on clinical and socioeconomic questionnaire, Autism Treatment Evaluation Checklist (ATEC), Childhood Autism Rating Scale (CARS) and Vineland 3 Scale. The Brief Symptom Inventory (BSI) was applied to evaluate caregiver's health. RESULTS: Sixteen patients with ASD who received cannabinoid treatment (CBD group) and seventeen patients with ASD without cannabinoid treatment (control group). CBD group was characterized as severe autism, ATEC total (SD) 85.5 ± 34.00, while controls as moderate, ATEC total (SD) 58.6 ± 25.53 (p = 0.047). After 3 months of treatment, CBD group showed a reduction in maladaptive behavior - internalizing (Vineland 3) (p = 0.008), and their caregivers a reduction in symptoms of Interpersonal Sensitivity (BSI) (p = 0.038), Global Severity Index (BSI) (p = 0.025) and Positive Symptom Distress Index (BSI) (p = 0.007), indicating reduction on mental health symptoms. For the control group, after 3 months there was a significant increase in scores for Daily Living Activities (Vineland 3) (p = 0.031) and Socialization (ATEC) (p = 0.037). CONCLUSION: This study suggests that therapy with cannabidiol (CBD)-rich extract in severe ASD may have positive effects on anxious and depressive symptoms, potentially positively impacting on the mental health of their caregivers.
Philopsychedelia beyond the West: The decolonial reflorescence of psychedelic philosophy.
Costa de Freitas JC, Medeiros Maia NC, da Silva Shanenawa MB … +2 more , Amaringo JV, Martinez RA
Prog Brain Res · 2025 · PMID 40967682 · Publisher ↗
The main purpose of this work is to identify the intersections between decolonial thought and psychedelic philosophy. By "psychedelic" we mean a pharmacological category, the effects of substances that modulates percepti...
The main purpose of this work is to identify the intersections between decolonial thought and psychedelic philosophy. By "psychedelic" we mean a pharmacological category, the effects of substances that modulates perception, a myriad of consciousness states, a set of ecstatic practices, a variety of countercultural movements, a constellation of artistic avant-gardes, and a plurality of ways of being. We thus intend to demonstrate how visionary aesthetics, liminal phenomenologies, ancestral epistemologies, ethics of resistance, politics of freedom and kaleidoscopic metaphysics are conceptual horizons from which a decolonization of the "manifestations of the mind" can come to light. Through an analytical-descriptive methodology, we idealize obtaining, as a result of this research, a philosophical justification of the indispensability of integrating decoloniality into the reflorescence of psychedelia. In a nutshell: we envision to clarify the extent to which psychedelic experiences can be ways of understanding insurgent knowledges, as well as explaining the proportion to which decolonial conceptions can be keys to interpreting psychedelic experiences.
Expressive resource in a clinical psychedelic study: Art as an integration tool.
Barros H, Falchi-Carvalho M, Maia LO … +5 more , Laborde S, Palhano-Fontes F, Wießner I, Arruda-Sanchez T, Araujo DB
Prog Brain Res · 2025 · PMID 40967681 · Publisher ↗
Psychedelic experiences, especially those induced by substances such as N,N-Dimethyltryptamine (DMT), are often characterized by high subjective intensity, complex visual content, and notable ineffability-that is, the di...
Psychedelic experiences, especially those induced by substances such as N,N-Dimethyltryptamine (DMT), are often characterized by high subjective intensity, complex visual content, and notable ineffability-that is, the difficulty of being fully expressed in words. This expressive limitation poses a significant challenge to the integration of the experience, which is essential for the therapeutic processing of these experiences. In this context, clinical studies with psychedelics are increasingly demanding innovative approaches to facilitate the assimilation of such experiences into daily life. Art, as a form of nonverbal expression, has been proposed as a promising tool in this regard. Accordingly, this article discusses the use of the mandala as a complementary expressive resource in the process of psychedelic integration, based on a Phase I clinical trial with DMT. The analysis draws on the mandalas and narratives produced by participants. The findings suggest that the creation of mandalas facilitated the symbolic expression of subjective content that was difficult to verbalize, supporting the integration process. Despite its potential, the use of expressive tools remains underexplored and unsystematized in current psychedelic clinical protocols. We concluded that the inclusion of art may represent a valuable advancement in optimizing the therapeutic benefits of psychedelics, expanding the understanding and meaning of experience.
Psychedelic-assisted therapies for existential and spiritual suffering in palliative care.
Garcia ACM, Maia LO
Prog Brain Res · 2025 · PMID 40967680 · Publisher ↗
Existential and spiritual suffering are frequently reported by individuals facing serious illnesses, particularly at the end of life, and are associated with diminished quality of life, increased psychological distress,...
Existential and spiritual suffering are frequently reported by individuals facing serious illnesses, particularly at the end of life, and are associated with diminished quality of life, increased psychological distress, and requests for hastened death. While Palliative Care (PC) aims to provide holistic support, existing therapeutic options often fail to adequately address the profound disruptions in meaning, connection, and dignity experienced by patients. Psychedelic-Assisted Therapies (PAT), notably those using psilocybin, have re-emerged as promising interventions capable of eliciting transformative experiences that may alleviate existential and spiritual distress. This chapter explores the potential role of PAT in PC, beginning with a historical and conceptual overview of PC and an analysis of existential and spiritual suffering in this context. It then reviews scientific evidence on the therapeutic applications of classical psychedelics, with a focus on existential and spiritual suffering. Practical, clinical, ethical, and legal considerations for the integration of PAT into PC are discussed, including the challenges of implementation and the need for spiritually and existentially informed treatment models. The chapter concludes by reinforcing the urgency of innovative and compassionate responses to existential suffering and highlighting PAT as an emerging pathway toward improving the quality of life-and death-of individuals with serious illnesses.
Chemical diversity, receptor binding affinity, and pharmacology of phytocannabinoids: Insights into neuronal mechanisms.
Queiroz CM, de Oliveira Koren L, da Silva CRP … +2 more , Ribeiro S, Silva SRB
Prog Brain Res · 2025 · PMID 40967679 · Publisher ↗
Comparative studies of phytocannabinoids offer valuable insights into the therapeutic potential of cannabis. While Cannabis sativa can produce over 100 distinct phytocannabinoids, most are present only in trace amounts....
Comparative studies of phytocannabinoids offer valuable insights into the therapeutic potential of cannabis. While Cannabis sativa can produce over 100 distinct phytocannabinoids, most are present only in trace amounts. This review examines the structural, biochemical, and pharmacological characteristics of five representative phytocannabinoids: cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (Δ-THC), and cannabinol (CBN). We describe their biosynthetic pathways, abiotic transformations, and precursor roles in generating molecular diversity. Chemovar profiles are discussed based on seed bank data and chromatographic analyses of Brazilian-grown cultivars. Our findings suggest that high-CBD chemovars have recently emerged, possibly due to genetic drift from intensive hybridization. To evaluate the clinical relevance of these compounds, we conducted a systematic review and meta-analysis of binding affinities (Ki) for CB1, CB2, and other neuronal receptors. Δ-THC and CBN showed high affinities for CB1 and CB2, while CBG, CBC, and CBD exhibited 10-100 times lower affinities. Statistical analysis confirmed significantly stronger CB1 and CB2 binding for Δ-THC compared to CBD. These results support the hypothesis that non-psychotropic phytocannabinoids primarily act through non-canonical targets such as GPR55 (G Protein-Coupled Receptor 55), TRPV1 (Transient Receptor Potential Vanilloid 1), and TRPM8 (Transient Receptor Potential Melastatin 8), though affinity data for these receptors remain limited. Finally, we discuss preclinical pharmacological evidence highlighting how subtle structural differences yield distinct physiological effects. Our findings emphasize the need for expanded research into underexplored phytocannabinoids with unique therapeutic potential.
Preface.
Kawamoto EM, Scavone C, Camarini R
Prog Brain Res · 2025 · PMID 40769647 · Publisher ↗
Abstract loading — click title to view on PubMed.
Impacts of aging on brain metabolism.
Rodrigues BA, Pretes TCS, do Nascimento Silva J
Prog Brain Res · 2025 · PMID 40769646 · Publisher ↗
Changes in energy homeostasis in aging have significant implications for brain health. Decreased glucose utilization efficiency, mitochondrial dysfunction, loss of metabolic flexibility, and increased oxidative stress ca...
Changes in energy homeostasis in aging have significant implications for brain health. Decreased glucose utilization efficiency, mitochondrial dysfunction, loss of metabolic flexibility, and increased oxidative stress can compromise cognitive functions and increase vulnerability to neurodegenerative diseases. Understanding these changes provides valuable insights for prevention and treatment strategies, such as dietary interventions, physical exercise, and pharmacological therapies, aimed at restoring or preserving energy homeostasis in the brain and thus improving cognitive health throughout life. This chapter explores the metabolic changes in the brain associated with aging, examining the underlying biochemical and molecular mechanisms, as well as therapeutic strategies that may alleviate the detrimental effects of brain aging.
Exercise for brain health: From cells to circuits.
Vivar C, Orihuela LP, Apostol G
Prog Brain Res · 2025 · PMID 40769645 · Publisher ↗
Exercise has been central to human brain evolution. Genus Homo was a nomadic species that constantly explored novel environments, which requires the encoding of new spatial and contextual patterns and the consolidation a...
Exercise has been central to human brain evolution. Genus Homo was a nomadic species that constantly explored novel environments, which requires the encoding of new spatial and contextual patterns and the consolidation and recall of details to localize potential food and avoid danger, functions associated with the hippocampus. Interestingly, no primates other than humans run long distances over extended periods using aerobic metabolism, a capacity described as endurance running (ER). It has been hypothesized that ER capacity may have had relevant effects on the evolution of brain structure and cognition in the genus Homo. Paradoxically, modern humans have become sedentary and no longer need to run for food or survival. The lack of exercise in the population has increased the risk of brain disorders. Studies in human and animal models show that exercise elicits functional and structural changes throughout the brain, which may serve as a mechanism to counteract the changes induced by aging and reduced physical activity. Here, we describe the cortico-hippocampal circuitry and summarize evidence from human and animal models of aging-induced and exercise-induced changes in cortical and subcortical areas that provide polymodal information and modulatory inputs to the hippocampus, respectively. We discuss how exercise-induced plasticity in the cortico-hippocampal circuit may improve brain health.
Intermittent fasting and ketone bodies.
Oliveira Dos Santos GR, de Souza Lima TA, Gallus M … +1 more , Kawamoto EM
Prog Brain Res · 2025 · PMID 40769644 · Publisher ↗
Intermittent fasting (IF) is a dietary intervention based on time-restricted energy intake. Over the years, IF has been widely investigated as a non-pharmacological approach to increasing life expectancy and promoting br...
Intermittent fasting (IF) is a dietary intervention based on time-restricted energy intake. Over the years, IF has been widely investigated as a non-pharmacological approach to increasing life expectancy and promoting brain health. The underlying mechanisms by which IF promotes its beneficial effects are attributed to hormesis, an evolutionary adaptive strategy that regulates cellular responses to stress. These effects include elevated levels of brain-derived neurotrophic factor (BDNF), enhanced neurogenesis and autophagy, increased synaptic plasticity, and improved cognitive functions such as memory and learning. The metabolic switch induced by IF promotes the production of ketone bodies (β-hydroxybutyrate, acetoacetate, and acetone), which serve as alternative energy substrate for the central nervous system (CNS) and modulator of vital processes, including cellular homeostasis, inflammation, and oxidative stress. The two most common neurodegenerative diseases, Alzheimer's Disease (AD) and Parkinson's Disease (PD), are characterized by mitochondrial dysfunction, neuroinflammation and energy deficits. IF has shown a promising therapeutic approach through its neuroprotective and anti-inflammatory effects, which need to be further assessed. Through similar mechanisms, IF appears to exert an antidepressant effect by regulating monoamines in limbic regions, and inhibiting neuroinflammation.
Hormesis and cancer therapy.
Machado-Santelli GM, Chaves JB
Prog Brain Res · 2025 · PMID 40769643 · Publisher ↗
Hormesis, the processes in which small doses of a stressor show stimulatory effects or protective responses on target cells, and high doses show the opposite effects, was described as associated with cancer therapy. Alth...
Hormesis, the processes in which small doses of a stressor show stimulatory effects or protective responses on target cells, and high doses show the opposite effects, was described as associated with cancer therapy. Although the introduction of new techniques in cancer therapy improved the success rate and patients' survival, it is important to mainly focus on chemo and radiotherapy. Some examples illustrating the hormetic relationships with cancer therapy are described. The hormetic response in cancer therapy presents considerable complexity due to the wide variability in biological responses observed between different systems and conditions. This variability poses significant challenges for the practical implementation of hormesis in oncological settings. Nevertheless, its potential to optimize existing therapies positions this phenomenon as an area of great interest and relevance for future scientific investigations.
Hormesis and brain metabolism in aging and neurodegeneration.
Pereira RM, Albernaz-Mariano KA, Jucá PM … +3 more , Juliano VAL, Sampaio LL, Munhoz CD
Prog Brain Res · 2025 · PMID 40769642 · Publisher ↗
This chapter explores sex-specific differences in brain development and hormones' critical role throughout life. Understanding these variabilities is vital for mental health, particularly concerning stress responses, agi...
This chapter explores sex-specific differences in brain development and hormones' critical role throughout life. Understanding these variabilities is vital for mental health, particularly concerning stress responses, aging, and the risk of neurodegenerative and cardiometabolic diseases. We examine the biological mechanisms involved, highlighting how hormones affect brain formation, neuronal plasticity, and stress responses, focusing on male and female variations. Research from animal studies and human data shows that males and females have distinct susceptibilities to diseases influenced by sex-specific hormonal effects on genes, cellular functions, and energy metabolism. Additionally, we examine the role of glucocorticoids in these diseases, considering their sex-specific effects on normal and dysfunctional physiological processes. A closer look at hormonal transition periods-such as early childhood, puberty, and menopause-emphasizes the need for sex-specific strategies in research and treatment. Overall, this chapter underscores the importance of understanding the interplay between biological sex, hormonal changes, and environmental stressors throughout life, as these factors significantly impact the onset and progression of various health conditions. Tailored approaches in health research and treatment are advocated to better address these differences.
Hormesis-induced neuroplasticity: Targeting neuroinflammation signaling cascades for therapeutic insights in aging and neurodegenerative diseases.
Santiago Pretes TC, Scavone C
Prog Brain Res · 2025 · PMID 40769641 · Publisher ↗
The signaling pathways associated with α-Klotho, glutamate, mediators of the inflammatory response in the central nervous system (CNS) and that related to different isoforms of the Na, K-ATPase (NKA) protein as a pump an...
The signaling pathways associated with α-Klotho, glutamate, mediators of the inflammatory response in the central nervous system (CNS) and that related to different isoforms of the Na, K-ATPase (NKA) protein as a pump and receptor for endogenous steroids (ouabain-like hormones) are associated with neuroplasticity and neuroprotection. This neuroadaptive response induced by pharmacologic (Cardiotonic Steroids, Klotho, Resveratrol, Curcumin, and other Phytochemicals), and non-pharmacologic strategies (intermittent fasting and physical exercise) involves glial and neuronal cell crosstalk through activation of different intracellular pathways involving mediators, such as glutamate, cytokines, transcription factors, and gene expression which will exert a marked influence on the adaptive processes (neuroplasticity) that prevent premature aging, in addition to playing an essential role in cognition and neurodegenerative processes. The present text addresses the effect of these agents on the Central Nervous System (CNS), exploring neuroplasticity changes associated with the neuroinflammation induced by these mediators in the presence of a modified expression or signaling of the α-Klotho and the different α-isoforms of NKA. The studies involve in vitro approaches using models of neuronal and glial cells and in vivo studies with a behavioral and biochemical approach. Studies were also done in the presence (or absence) of changes in the expression of these proteins (by using vectors, interference RNA, and transgenic animals with specific protein-modified expression, such as TNF-α and Klotho). It has been also several human studies evaluating these hermetic strategies associated with physical exercise and intermittent diet. The present chapter discusses the benefit of these strategies in the induction of neuroadaptive response.
Hormesis and brain diseases.
Lim VJT, Tabassum NI, Orian JM … +2 more , Arumugam TV, Weng EF
Prog Brain Res · 2025 · PMID 40769640 · Publisher ↗
Hormesis, the concept that low doses of potentially harmful stressors can elicit adaptive, beneficial effects, plays a significant role in brain health and aging. Neurohormesis refers to the adaptive response of neurons...
Hormesis, the concept that low doses of potentially harmful stressors can elicit adaptive, beneficial effects, plays a significant role in brain health and aging. Neurohormesis refers to the adaptive response of neurons to mild stress, activating pathways that enhance cellular repair. As the brain ages, it experiences disruptions in energy metabolism, oxidative stress, mitochondrial dysfunction, and chronic inflammation, all of which contribute to neurodegenerative diseases like stroke, Parkinson's, Alzheimer's and multiple sclerosis (MS). However, low-dose stressors such as exercise, fasting, and certain dietary compounds have been shown to activate stress-resilience mechanisms, promoting brain health and delaying neurodegeneration. Dietary interventions, such as calorie restriction (CR) and intermittent fasting (IF), stimulate neuroprotective signaling, involving molecular targets like NF-E2-related factor 2 (NRF2), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF). These factors regulate stress-related chaperones and promote cognitive function. The chapter highlights the role of mitochondrial health, autophagy, and circadian rhythms in aging and neurohormesis by CR and IF. Despite the potential of hormetic interventions, aging impairs the capacity of the brain to respond to stress, making it more vulnerable to neurodegeneration. Understanding neurohormesis offers promising therapeutic avenues for enhancing brain resilience and delaying the onset of age-related cognitive decline and neurodegenerative diseases. The integration of advanced technologies, such as multi-omics and epigenetic studies, could further elucidate the protective effects of hormesis on brain health, paving the way for targeted interventions to combat neurodegeneration.
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