Microvascular alterations within and outside the central nervous system(CNS)in amyotrophic lateral sclerosis(ALS):ALS is a fatal neurodegenerative disease leading to paralysis and eventual death within 3 to 5 years of...Microvascular alterations within and outside the central nervous system(CNS)in amyotrophic lateral sclerosis(ALS):ALS is a fatal neurodegenerative disease leading to paralysis and eventual death within 3 to 5 years of diagnosis due to respiratory dysfunction.Numerous pathogenic intrinsic and extrinsic effectors are involved in the diffuse motor neuron degeneration.Also,impairment of neurovascular unit components in the brain and spinal cord in ALS patients and in animal models of disease was noted and points to vascular pathology being a key factor in the recognition of ALS as a neurovascular disease(Garbuzova-Davis et al.,2011).展开更多
Amyotrophic lateral sclerosis(ALS)is a rapidly fatal neurological disease characterized by upper and lower motor neuron degeneration.Though typically idiopathic,familial forms of ALS are commonly composed of a superox...Amyotrophic lateral sclerosis(ALS)is a rapidly fatal neurological disease characterized by upper and lower motor neuron degeneration.Though typically idiopathic,familial forms of ALS are commonly composed of a superoxide dismutase 1(SOD1)mutation.Basic science frequently utilizes SOD1 models in vitro and in vivo to replicate ALS conditions.Therapies are sparse;those that exist in the market extend life minimally,thus driving the demand for research to identify novel therapeutics.Transplantation of stem cells is a promising approach for many diseases and has shown efficacy in SOD1 models and clinical trials.The underlying mechanism for stem cell therapy presents an exciting venue for research investigations.Most notably,the paracrine actions of stem cell-derived extracellular vesicles(EVs)have been suggested as a potent mitigating factor.This literature review focuses on the most recent preclinical research investigating cellfree methods for treating ALS.Various avenues are being explored,differing on the EV contents(protein,microRNA,etc.)and on the cell target(astrocyte,endothelial cell,motor neuron-like cells,etc.),and both molecular and behavioral outcomes are being examined.Unfortunately,EVs may also play a role in propagating ALS pathology.Nonetheless,the overarching goal remains clear:to identify efficient cell-free techniques to attenuate the deadly consequences of ALS.展开更多
基金This work was supported by the National Instites of Health,National Institute of Neurological Disorders and Stroke(1R01NS090962).
文摘Microvascular alterations within and outside the central nervous system(CNS)in amyotrophic lateral sclerosis(ALS):ALS is a fatal neurodegenerative disease leading to paralysis and eventual death within 3 to 5 years of diagnosis due to respiratory dysfunction.Numerous pathogenic intrinsic and extrinsic effectors are involved in the diffuse motor neuron degeneration.Also,impairment of neurovascular unit components in the brain and spinal cord in ALS patients and in animal models of disease was noted and points to vascular pathology being a key factor in the recognition of ALS as a neurovascular disease(Garbuzova-Davis et al.,2011).
文摘Amyotrophic lateral sclerosis(ALS)is a rapidly fatal neurological disease characterized by upper and lower motor neuron degeneration.Though typically idiopathic,familial forms of ALS are commonly composed of a superoxide dismutase 1(SOD1)mutation.Basic science frequently utilizes SOD1 models in vitro and in vivo to replicate ALS conditions.Therapies are sparse;those that exist in the market extend life minimally,thus driving the demand for research to identify novel therapeutics.Transplantation of stem cells is a promising approach for many diseases and has shown efficacy in SOD1 models and clinical trials.The underlying mechanism for stem cell therapy presents an exciting venue for research investigations.Most notably,the paracrine actions of stem cell-derived extracellular vesicles(EVs)have been suggested as a potent mitigating factor.This literature review focuses on the most recent preclinical research investigating cellfree methods for treating ALS.Various avenues are being explored,differing on the EV contents(protein,microRNA,etc.)and on the cell target(astrocyte,endothelial cell,motor neuron-like cells,etc.),and both molecular and behavioral outcomes are being examined.Unfortunately,EVs may also play a role in propagating ALS pathology.Nonetheless,the overarching goal remains clear:to identify efficient cell-free techniques to attenuate the deadly consequences of ALS.
