The human brain is unique in its relative size, cellular diversity and cytoarchitecture, coding and non-coding gene expression patterns, neurotransmitter pathways and functions, expanded association cortices, and metabolic rates. One critical species-distinctive feature of the human brain is its prolonged and complex developmental processes, which begin in utero and continue through childhood, adolescence, and early adulthood. Compared to other species—including other primates—human brain development involves highly complex spatiotemporal dynamics, numerous distinct cellular diversification trajectories, and lengthier periods of neuronal proliferation, functional and structural plasticity, connectivity, and myelination.The protracted and intricate nature of human neurodevelopment increases our social, cognitive, and emotional capacity, complexity, and flexibility. However, it also increases the susceptibility of the human brain to environmental, genetic, and epigenetic influences across the lifespan, and subsequently, our susceptibility to neurodevelopmental disorders and neurodegenerative diseases. These conditions, including Alzheimer’s disease, Parkinson’s disease, autism spectrum disorders, Huntington’s disease, multiple sclerosis, attention-deficit disorders, and amyotrophic lateral sclerosis affect more than 250 million people worldwide. Current projections estimate the prevalence of these debilitating conditions will increase significantly in the coming decades.The devastating impact of these conditions on individuals and their families, the burden to healthcare systems, and their high prevalence have prompted the allocation of substantial resources to research dedicated to understanding the underlying mechanisms of these diseases and to developing new treatments. However, despite this considerable investment, understanding disease pathways and developing effective new therapeutics for these neurological conditions proves challenging, primarily due to the difficulty studying early human brain development in vivo using traditional research methods and the inability to recapitulate key species-specific characteristics of human brain maturation in animals.Growing awareness of the limitations of using animals to study human neurological conditions and continuing advancements in human-derived iPSC models, neuroimaging tools, and -omics technologies are driving a paradigm shift in how we study human neurodevelopment, neurodevelopmental disorders, and neurodegenerative disease.These innovative approaches are transforming our understanding of human brain maturation and its disorders, and this Research Topic will highlight and integrate the latest advancements in our understanding of neurological disease emerging from innovative, human-relevant research and discuss future directions in this field. Priority will be given to submissions investigating the impact of environmental, genetic, and/or epigenetic disruption on cellular, molecular, structural, and functional maturation as well as the homeostasis and integrity of the human brain across the lifespan using non-invasive neuroimaging tools, diagnostic tools based on peripheral biomarkers, large-scale epidemiological data, multi-omics technologies, and/or sophisticated human-derived in vitro tools.This project aims to highlight research investigating human-specific neurological changes across the lifespan and their role in our increased vulnerabilities to neurological disease, with emphasis on the following:• Research using sophisticated in vitro tools capable of identifying human-specific early developmental mechanisms typically inaccessible for study with post-mortem tissue or in vivo in humans.• Research into the importance of disruptions during adolescence or other developmental stages not commonly investigated due to their poor representation in nonhuman animals.• Innovative, human-relevant research tools exploring the roles of chronic systemic inflammation, the microbiota-gut-brain axis, mitochondrial dysfunction, mitophagy as well as autophagy, and/or stress resilience across the human lifespan to elucidate neurological disease mechanisms.• Research into the complex role of sex and sex hormones as risk factors for the development of neurodegenerative disease.• Research investigating the role of latent virus infections (Herpes Simplex, EBV, CMV, Covid-19) on the development of human neurodegenerative disease.• Research addressing epigenetic mechanisms that influence disease susceptibility in humans across different developmental stages.• Research using human-centric data to identify neurological disease prevention strategies.• Review articles addressing the limitations of animal models for human neurodegenerative disease research.Dr. Erwin Roggen is employed by ToxGenSolutions and Dr. Katherine Roe is employed by PETA. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
The human brain is unique in its relative size, cellular diversity and cytoarchitecture, coding and non-coding gene expression patterns, neurotransmitter pathways and functions, expanded association cortices, and metabolic rates. One critical species-distinctive feature of the human brain is its prolonged and complex developmental processes, which begin in utero and continue through childhood, adolescence, and early adulthood. Compared to other species—including other primates—human brain development involves highly complex spatiotemporal dynamics, numerous distinct cellular diversification trajectories, and lengthier periods of neuronal proliferation, functional and structural plasticity, connectivity, and myelination.The protracted and intricate nature of human neurodevelopment increases our social, cognitive, and emotional capacity, complexity, and flexibility. However, it also increases the susceptibility of the human brain to environmental, genetic, and epigenetic influences across the lifespan, and subsequently, our susceptibility to neurodevelopmental disorders and neurodegenerative diseases. These conditions, including Alzheimer’s disease, Parkinson’s disease, autism spectrum disorders, Huntington’s disease, multiple sclerosis, attention-deficit disorders, and amyotrophic lateral sclerosis affect more than 250 million people worldwide. Current projections estimate the prevalence of these debilitating conditions will increase significantly in the coming decades.The devastating impact of these conditions on individuals and their families, the burden to healthcare systems, and their high prevalence have prompted the allocation of substantial resources to research dedicated to understanding the underlying mechanisms of these diseases and to developing new treatments. However, despite this considerable investment, understanding disease pathways and developing effective new therapeutics for these neurological conditions proves challenging, primarily due to the difficulty studying early human brain development in vivo using traditional research methods and the inability to recapitulate key species-specific characteristics of human brain maturation in animals.Growing awareness of the limitations of using animals to study human neurological conditions and continuing advancements in human-derived iPSC models, neuroimaging tools, and -omics technologies are driving a paradigm shift in how we study human neurodevelopment, neurodevelopmental disorders, and neurodegenerative disease.These innovative approaches are transforming our understanding of human brain maturation and its disorders, and this Research Topic will highlight and integrate the latest advancements in our understanding of neurological disease emerging from innovative, human-relevant research and discuss future directions in this field. Priority will be given to submissions investigating the impact of environmental, genetic, and/or epigenetic disruption on cellular, molecular, structural, and functional maturation as well as the homeostasis and integrity of the human brain across the lifespan using non-invasive neuroimaging tools, diagnostic tools based on peripheral biomarkers, large-scale epidemiological data, multi-omics technologies, and/or sophisticated human-derived in vitro tools.This project aims to highlight research investigating human-specific neurological changes across the lifespan and their role in our increased vulnerabilities to neurological disease, with emphasis on the following:• Research using sophisticated in vitro tools capable of identifying human-specific early developmental mechanisms typically inaccessible for study with post-mortem tissue or in vivo in humans.• Research into the importance of disruptions during adolescence or other developmental stages not commonly investigated due to their poor representation in nonhuman animals.• Innovative, human-relevant research tools exploring the roles of chronic systemic inflammation, the microbiota-gut-brain axis, mitochondrial dysfunction, mitophagy as well as autophagy, and/or stress resilience across the human lifespan to elucidate neurological disease mechanisms.• Research into the complex role of sex and sex hormones as risk factors for the development of neurodegenerative disease.• Research investigating the role of latent virus infections (Herpes Simplex, EBV, CMV, Covid-19) on the development of human neurodegenerative disease.• Research addressing epigenetic mechanisms that influence disease susceptibility in humans across different developmental stages.• Research using human-centric data to identify neurological disease prevention strategies.• Review articles addressing the limitations of animal models for human neurodegenerative disease research.Dr. Erwin Roggen is employed by ToxGenSolutions and Dr. Katherine Roe is employed by PETA. All other Topic Editors declare no competing interests with regards to the Research Topic subject.