scholarly journals Region-Specific Protein Abundance Changes in the Brain of MPTP-Induced Parkinson’s Disease Mouse Model

2010 ◽  
Vol 9 (3) ◽  
pp. 1496-1509 ◽  
Author(s):  
Xu Zhang ◽  
Jian-Ying Zhou ◽  
Mark H. Chin ◽  
Athena A. Schepmoes ◽  
Vladislav A. Petyuk ◽  
...  
2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Nandhini Kanagaraj ◽  
S Thameem Dheen ◽  
Zhao Feng Peng ◽  
Dinesh Kumar Srinivasan ◽  
Samuel S W Tay

Author(s):  
Emily Clarke ◽  
Liz Sinclair ◽  
Edward J R Fletcher ◽  
Alicja Krawczun-Rygmaczewska ◽  
Susan Duty ◽  
...  

AbstractSingle domain shark antibodies that bind to the transferrin receptor 1 (TfR1) on brain endothelial cells can be used to shuttle antibodies and other cargos across the blood brain barrier (BBB). We have fused one of these (TXB4) to differing regions of TrkB and TrkC neurotrophin receptor agonist antibodies (AAb) and determined the effect on agonist activity, brain accumulation and engagement with neurons in the mouse brain following systemic administration. The TXB4-TrkB and TXB4-TrkC fusion proteins retain agonist activity at their respective neurotrophin receptors and in contrast to their parental AAb they rapidly accumulate in the brain reaching nM levels following a single IV injection. Following SC administration, the most active TrkB fusion protein, TXB4-TrkB1, associates with and activates ERK1/2 signalling in TrkB positive cells in the cortex and tyrosine hydroxylase (TH) positive dopaminergic neurons in the substantia nigra pars compacta (SNc). When tested in the 6-hydroxydopamine (6-OHDA) mouse model of Parkinson’s disease (PD) TXB4-TrkB1, but not the parental TrkB AAb or a TXB4-TrkC1 fusion protein, completely prevented the 6-OHDA induced death of TH positive neurons in the SNc. In conclusion, the fusion of the TXB4 TfR1 binding module allows a TrkB AAb to reach neuroprotective concentrations in the brain parenchyma following systemic administration.


2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
meenalochani sivasubramanian ◽  
S Thameem Dheen ◽  
Zhao Feng Peng ◽  
Dinesh Kumar Srinivasan ◽  
Samuel SW Tay

2019 ◽  
Vol 10 (10) ◽  
pp. 4337-4349 ◽  
Author(s):  
Oleg V. Ardashov ◽  
Alla V. Pavlova ◽  
Arun Kumar Mahato ◽  
Yulia Sidorova ◽  
Ekaterina A. Morozova ◽  
...  

2021 ◽  
Vol 22 (23) ◽  
pp. 12616
Author(s):  
Sangeun Han ◽  
Min Hyung Seo ◽  
Sabina Lim ◽  
Sujung Yeo

We investigated the potential association between integrin α7 (ITGA7) and alpha-synuclein (α-syn) in a methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) mouse model. Tyrosine hydroxylase (TH), ITGA7, and α-syn expression in the substantia nigra (SN) of the brain were observed to examine the pathological characteristics of PD. To determine the relationship between ITGA7 and PD, the expression of TH and α-syn was investigated after ITGA7 siRNA knockdown in SH-SY5Y cells. The ITGA7 microarray signal was decreased in the SN of the MPTP group, indicating reduced ITGA7 expression compared to that in the control. The expression patterns of ITGA7 in the control group and those of α-syn in the MPTP group were similar on immunohistochemical staining. Reduction in ITGA7 expression by ITGA7 siRNA administration induced a decrease in TH expression and an increase in α-syn expression in SH-SY5Y cells. The decreased expression of ITGA7 significantly decreased the expression of bcl2 and increased the bax/bcl2 ratio in SH-SY5Y cells. These results suggest that reduced ITGA7 expression may be related to increased α-syn expression and apoptosis of dopaminergic cells in an MPTP-induced PD mouse model. To the best of our knowledge, this is the first study to show an association between ITGA7 and PD.


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