SYNGR4 and PLEKHB1 deregulation in motor neurons of amyotrophic lateral sclerosis models: potential contributions to pathobiology  

作　　者：Rita F.Marques Kent E.Duncan 

机构地区：[1]Institute for Biochemistry and Molecular Biology,Department of Chemistry,University of Hamburg,Hamburg,Germany [2]Neuronal Translational Control Research Group,Center for Molecular Neurobiology Hamburg(ZMNH),University Medical Center Hamburg-Eppendorf,Hamburg,Germany

出　　处：《Neural Regeneration Research》2022年第2期266-270,共5页中国神经再生研究（英文版）

基　　金：supported in part by funding from the Else Kr?ner Fresenius Stiftung(Co-PI);the Werner Otto Stiftung(PI)(to KED)。

摘　　要：Amyotrophic lateral sclerosis is the most common adult-onset neurodegenerative disease affecting motor neurons. Its defining feature is progressive loss of motor neuron function in the cortex, brainstem, and spinal cord, leading to paralysis and death. Despite major advances in identifying genes that can cause disease when mutated and model the disease in animals and cellular models, it still remains unclear why motor symptoms suddenly appear after a long pre-symptomatic phase of apparently normal function. One hypothesis is that age-related deregulation of specific proteins within key cell types, especially motor neurons themselves, initiates disease symptom appearance and may also drive progressive degeneration. Genome-wide in vivo cell-type-specific screening tools are enabling identification of candidates for such proteins. In this minireview, we first briefly discuss the methodology used in a recent study that applied a motor neuron-specific RNASeq screening approach to a standard model of TAR DNA-binding protein-43(TDP-43)-driven amyotrophic lateral sclerosis. A key finding of this study is that synaptogyrin-4 and pleckstrin homology domain-containing family B member 1 are also deregulated at the protein level within motor neurons of two unrelated mouse models of mutant TDP-43 driven amyotrophic lateral sclerosis. Guided by what is known about molecular and cellular functions of these proteins and their orthologs, we outline here specific hypotheses for how changes in their levels might potentially alter cellular physiology of motor neurons and detrimentally affect motor neuron function. Where possible, we also discuss how this information could potentially be used in a translational context to develop new therapeutic strategies for this currently incurable, devastating disease.

关 键 词：amyotrophic lateral sclerosis glucagon-like peptide-1 receptor motor neuron disease mouse model NEURODEGENERATION PHOSPHATIDYLSERINE pleckstrin homology domain synaptogyrin TAR DNA-binding protein-43 vesicle transport 

分 类 号：R744.8[医药卫生—神经病学与精神病学]