After an insult of white matter tracts,e.g.in the spinal cord or optic nerve,axons react in general by the activation of a tightly regulated self-destruction program.This so-called axon degeneration cascade can be tri...After an insult of white matter tracts,e.g.in the spinal cord or optic nerve,axons react in general by the activation of a tightly regulated self-destruction program.This so-called axon degeneration cascade can be triggered by various causes,including injury,toxins,and genetic defects,and is a shared pathway in many different neurological diseases(Coleman and Hoke,2020).Axonal degeneration is thought to be responsible for disease progression and accumulation of disability across many neurological conditions.The hallmark of early axonal injury is the appearance of local spheroid formations along the axon,often referred to as a“pearl-on-string”pattern or axonal beading or swelling.Although this striking shape change has been observed after various types of injury,such as mechanical,chemical,or inflammatory stimuli,we know little about its exact mechanism and its immediate impact on axonal functionality.In this perspective,we would like to contrast the classical calcium-dependent form of axonal degeneration with a recently described form of a calcium-independent mechanism underlying axonal beading.展开更多
New neurons are generated throughout life in distinct areas of the mammalian brain. This process, called adult neurogenesis, has challenged previously held concepts about adult brain plasticity and opened novel therap...New neurons are generated throughout life in distinct areas of the mammalian brain. This process, called adult neurogenesis, has challenged previously held concepts about adult brain plasticity and opened novel therapeutic avenues to treat certain neuro-psychiatric diseases. Here, we review the current knowledge regarding the fate and potency of neural stem cells （NSCs）, as well as the mechanisms underlying neuronal differentiation and subsequent integration. Furthermore, we discuss the functional significance of adult neurogenesis in health and disease, and offer brief insight into the future directions of the adult neurogenesis field.展开更多
Background:Since the discovery of the induced pluripotent stem cell(iPSC)technique more than a decade ago,extensive progress has been made to develop clinically relevant cell culture systems.Alzheimer’s disease(AD)is...Background:Since the discovery of the induced pluripotent stem cell(iPSC)technique more than a decade ago,extensive progress has been made to develop clinically relevant cell culture systems.Alzheimer’s disease(AD)is the most common neurodegenerative disease,accounting for approximately two thirds of all cases of dementia.The massively increasing number of affected individuals explains the major interest of research in this disease as well as the strong need for better understanding of disease mechanisms.Main body:IPSC-derived neural cells have been widely used to recapitulating key aspects of AD.In this Review we highlight the progress made in studying AD pathophysiology and address the currently available techniques,such as specific differentiation techniques for AD-relevant cell types as well as 2D and 3D cultures.Finally,we critically discuss the key challenges and future directions of this field and how some of the major limitations of the iPSC technique may be overcome.Conclusion:Stem cell-based disease models have the potential to induce a paradigm shift in biomedical research.In particular,the combination of the iPSC technology with recent advances in gene editing or 3D cell cultures represents a breakthrough for in vitro disease modeling and provides a platform for a better understanding of disease mechanisms in human cells and the discovery of novel therapeutics.展开更多
文摘After an insult of white matter tracts,e.g.in the spinal cord or optic nerve,axons react in general by the activation of a tightly regulated self-destruction program.This so-called axon degeneration cascade can be triggered by various causes,including injury,toxins,and genetic defects,and is a shared pathway in many different neurological diseases(Coleman and Hoke,2020).Axonal degeneration is thought to be responsible for disease progression and accumulation of disability across many neurological conditions.The hallmark of early axonal injury is the appearance of local spheroid formations along the axon,often referred to as a“pearl-on-string”pattern or axonal beading or swelling.Although this striking shape change has been observed after various types of injury,such as mechanical,chemical,or inflammatory stimuli,we know little about its exact mechanism and its immediate impact on axonal functionality.In this perspective,we would like to contrast the classical calcium-dependent form of axonal degeneration with a recently described form of a calcium-independent mechanism underlying axonal beading.
文摘New neurons are generated throughout life in distinct areas of the mammalian brain. This process, called adult neurogenesis, has challenged previously held concepts about adult brain plasticity and opened novel therapeutic avenues to treat certain neuro-psychiatric diseases. Here, we review the current knowledge regarding the fate and potency of neural stem cells （NSCs）, as well as the mechanisms underlying neuronal differentiation and subsequent integration. Furthermore, we discuss the functional significance of adult neurogenesis in health and disease, and offer brief insight into the future directions of the adult neurogenesis field.
基金CT and SDL was supported by a grant from the Neuroscience Center Zurich,University of Zurich,Switzerland and from the Betty and David Koetser Foundation for Brain Research,Zurich,Switzerland.
文摘Background:Since the discovery of the induced pluripotent stem cell(iPSC)technique more than a decade ago,extensive progress has been made to develop clinically relevant cell culture systems.Alzheimer’s disease(AD)is the most common neurodegenerative disease,accounting for approximately two thirds of all cases of dementia.The massively increasing number of affected individuals explains the major interest of research in this disease as well as the strong need for better understanding of disease mechanisms.Main body:IPSC-derived neural cells have been widely used to recapitulating key aspects of AD.In this Review we highlight the progress made in studying AD pathophysiology and address the currently available techniques,such as specific differentiation techniques for AD-relevant cell types as well as 2D and 3D cultures.Finally,we critically discuss the key challenges and future directions of this field and how some of the major limitations of the iPSC technique may be overcome.Conclusion:Stem cell-based disease models have the potential to induce a paradigm shift in biomedical research.In particular,the combination of the iPSC technology with recent advances in gene editing or 3D cell cultures represents a breakthrough for in vitro disease modeling and provides a platform for a better understanding of disease mechanisms in human cells and the discovery of novel therapeutics.
