New perspectives on cytoskeletal dysregulation and mitochondrial mislocalization in amyotrophic lateral sclerosis  

作　　者：Frances Theunissen Phillip K.West Samuel Brennan Bojan Petrovic Kosar Hooshmand P.Anthony Akkari Matt Keon Boris Guennewig 

机构地区：[1]Perron Institute for Neurological and Translational Science,Nedlands,WA,Australia [2]Centre for Molecular Medicine and Innovative Therapeutics,Murdoch University,Murdoch,WA,Australia [3]GenieUs Genomics Pty Ltd,Sydney,NSW,Australia [4]Brain and Mind Centre and Central Clinical School,Faculty of Medicine and Health,the University of Sydney,amperdown,NSW,Australia [5]Division of Neurology,Duke University Medical Centre,Duke University,Durham,NC,USA

出　　处：《Translational Neurodegeneration》2021年第4期595-610,共16页转化神经变性病（英文）

基　　金：supported through the Australian National Health&Medical Research Council(NHMRC APP1163249).

摘　　要：Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease characterized by selective,early degeneration of motor neurons in the brain and spinal cord.Motor neurons have long axonal projections,which rely on the integrity of neuronal cytoskeleton and mitochondria to regulate energy requirements for maintaining axonal stability,anterograde and retrograde transport,and signaling between neurons.The formation of protein aggregates which contain cytoskeletal proteins,and mitochondrial dysfunction both have devastating effects on the function of neurons and are shared pathological features across several neurodegenerative conditions,including ALS,Alzheimer's disease,Parkinson's disease,Huntington's disease and Charcot-Marie-Tooth disease.Furthermore,it is becoming increasingly clear that cytoskeletal integrity and mitochondrial function are intricately linked.Therefore,dysregulations of the cytoskeletal network and mitochondrial homeostasis and localization,may be common pathways in the initial steps of neurodegeneration.Here we review and discuss known contributors,including variants in genetic loci and aberrant protein activities,which modify cytoskeletal integrity,axonal transport and mitochondrial localization in ALS and have overlapping features with other neurodegenerative diseases.Additionally,we explore some emerging pathways that may contribute to this disruption in ALS.

关 键 词：CYTOSKELETON NEUROFILAMENT Mitochondria Amyotrophic lateral sclerosis NEURODEGENERATION Axonal transport Gut microbiome 

分 类 号：R746.4[医药卫生—神经病学与精神病学]