Expression and Distribution of Arylsulfatase B are Closely Associated with Neuron Death in SOD1 G93A Transgenic Mice

Abstract

The known proteins only explained the partial pathogenesis of amyotrophic lateral sclerosis (ALS). Therefore, this study aimed to search the novel proteins possibly involved in ALS. In this study, we analyzed the expression and distribution of the candidate protein arylsulfatase B (ARSB) in the different segments, anatomic regions, and neural cells of spinal cord at the different stages of the wild-type and [Cu/Zn] superoxide dismutase 1 (SOD1) G93A transgenic mice using the fluorescent immunohistochemistry and the western blot. The results revealed that the ARSB was extensively expressed and distributed in the entire spinal cord; the expression and distribution of ARSB was significantly different in the different regions of spinal cord, the anterior horn of gray matter (AHGM) was significantly more than that in the posterior horn of gray matter (PHGM) and significantly more than that in the central canal, and ARSB was mainly distributed in the microglia and neuron cells in the wild-type mice. The expression of ARSB significantly increased in other anatomic regions besides the thoracic PHGM, significantly decreased at the progression stage, occurred in the redistribution from the AHGM and the PHGM to the central canal at the onset and progression stages, and no any alteration of ARSB expression and distribution occurred between the different neural cells in the SOD1 G93A mice compared with the wild-type mice. The increase of ARSB expression and distribution followed with the increased of neuron death. Our data suggested that the abnormal expression and distribution of ARSB were closely associated with the neuron death in the SOD1 G93A transgenic mice.

Preliminary Observation about Alteration of Proteins and Their Potential Functions in Spinal Cord of SOD1 G93A Transgenic Mice

“…Although we could not ensure that all significantly up regulated and down regulated proteins can be confirmed. Our better results 69 , 72 should confirm that our studied method and results were confident. Our results provided an important preliminary data for further studying the role of protein abnormality in the pathogenesis of ALS.…”

“…In the further studies, we confirmed some significantly up regulated and down regulated proteins by immunofluorescence histochemistry and western blot in spinal cord, brain and SOD1 G93A transfected PC12 cell lines. Among them, partial results have been published 69 , 72 , which were enough to confirm the reliability of our studying method. Although we could not ensure that all significantly up regulated and down regulated proteins can be confirmed.…”

HnRNP G Reduces Neuron Death in Amyotrophic Lateral Sclerosis by Preventing Abnormal TDP-43 Accumulation

“…It is obvious that hnRNP G has various and complex functions. Our studied groups found that the hnRNP G protein in the spinal cord of TG(SOD1*G93A)1Gur (TG) mice was signi cantly reduced through the methods of proteomic analysis [27]. The purpose of this study is to further explore the possible roles and mechanisms of hnRNP G in the pathogenesis of ALS.…”

“…The cellular cytotoxicity of mutants and/or cytoplasmic dislocated TDP-43 and FUS might be caused by the following reasons: (1) the loss of normal nuclear function leads to the disorder of nuclear RNA processing; (2) obtains the additional cytoplasmic RNA binding activity; (3) the polymerization dependent toxicity [7,[20][21][22]. More and more evidences show that the neurotoxicity generates through various cellular pathways, such as the RNA mismatch and the transcription reduction of c9orf72 gene, the disorder of transport between nuclear and cytoplasm, the stress of nuclear protein and DNA damage [23][24][25][26][27]. The break of DNA strand is the most serious types of DNA damage.…”

HnRNP G Reduces Neuron Death in Amyotrophic Lateral Sclerosis by Preventing Abnormal TDP-43 Accumulation

“…The cellular cytotoxicity of mutants and/or cytoplasmic dislocated TDP-43 and FUS might be caused by the following reasons: (1) the loss of normal nuclear function leads to the disorder of nuclear RNA processing; (2) obtains the additional cytoplasmic RNA binding activity; (3) the polymerization dependent toxicity [7,[20][21][22]. More and more evidence show that neurotoxicity generates through various cellular pathways, such as the RNA mismatch and the transcription reduction of c9orf72 gene, the disorder of transport between nuclear and cytoplasm, the stress of nuclear protein and DNA damage [23][24][25][26][27]. The break of DNA strand is the most serious type of DNA damage.…”