Rivastigmine is a clinical drug for patients of Alzheimer's disease (AD) exerting its inhibitory effect on acetylcholinesterase activity however, its effect on other disease-related pathological mechanisms are not yet known. This study was conducted to evaluate the effect of rivastigmine on protein aggregation and degradation related mechanisms employing streptozotocin (STZ) induced experimental rat model. The known inhibitory effect of rivastigmine on cognition and acetylcholinesterase activity was observed in both cortex and hippocampus and further its effect on tau level, amyloid aggregation, biochemical alterations, endoplasmic reticulum (ER) stress, calcium homeostasis, proteasome activity and apoptosis was estimated. STZ administration in rat brain caused significant cognitive impairment, augmented acetylcholinesterase activity, tau phosphorylation and amyloid aggregation which were significantly inhibited with rivastigmine treatment. STZ also caused significant biochemical alterations which were attenuated with rivastigmine treatment. Since AD pathology is related to protein aggregation and we have found disease-related amyloid aggregation, further the investigation was done to decipher the ER functionality and apoptotic signalling. STZ caused significantly altered level of ER stress related markers (GRP78, GADD153 and caspase-12) which were significantly inhibited with rivastigmine treatment. Furthermore, the effect of rivastigmine was estimated on proteasome activity in both regions. Rivastigmine treatment significantly enhances the proteasome activity and may contributes in removal of amyloid aggregation. In conclusion, findings suggested that along with inhibitory effect of rivastigmine on acetylcholinesterase activity and up to some extent on cognition, it has significant effect on disease-related biochemical alterations, ER functionality, protein degradation machinery and neuronal apoptosis.
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Cover Image
Cover Image
In this issue, Lee and colleagues (pp. 1471–1484) demonstrate a new mechanism for tau secretion potentially involved in neurodegenerative disease progression, involving syntaxins (STX) 6 and 8. The cover image shows immunostaining of primary mouse neurons transfected with eGFP-STX6 (green) and human V5-tau (red) with co-localization of V5-tau and eGFP-STX6 in secretory vesicles. Superimposed is a schematic illustrating the proposed transmembrane transfer of tau via STX6/8 TM, STX6 or STX8 into the trans-Golgi network (TGN) or recycling endosomes (RE) for subsequent secretion. The cover image was provided by Lars M Ittner.
Rivastigmine attenuates the Alzheimer's disease related protein degradation and apoptotic neuronal death signalling
Parul Gupta, Shubhangini Tiwari, Abhishek Singh, Amit Pal, Amit Mishra, Sarika Singh; Rivastigmine attenuates the Alzheimer's disease related protein degradation and apoptotic neuronal death signalling. Biochem J 16 April 2021; 478 (7): 1435–1451. doi: https://doi.org/10.1042/BCJ20200754
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