Jinjing Jia1, Xinhong Zhang2, Guangtao Xu3, Xiansi Zeng4, Li Li5. 1. Innovation Team of Neurobiology, Department of Physiology, Jiaxing University Medical College, Jiaxing, 314001, China. 2. Medical Experimental Center, Jiaxing University Medical College, Jiaxing, 314001, China. 3. Forensic and Pathology Laboratory, Jiaxing University Medical College, Jiaxing, 314001, China. 4. Innovation Team of Neurobiology, Department of Biochemistry and Molecular Biology, Jiaxing University Medical College, Jiaxing, 314001, China. zxs-2005@vip.163.com. 5. Innovation Team of Neurobiology, Department of Physiology, Jiaxing University Medical College, Jiaxing, 314001, China. Lily7588@163.com.
Abstract
BACKGROUND: Alzheimer's disease (AD), the most common neurodegenerative disease, is charactered by these accepted pathological features, such as β-amyloid (Aβ) plaques outside the neurons and neurofibrillary tangles inside the neurons. In recent years, several studies have demonstrated that pyroptosis is associated with the development of AD process. However, whether Aβ25-35 induces pyroptosis is still unclear. Thioredoxin-1 (Trx-1), an intracellular multifunctional protein, showed neuroprotective roles by inhibiting the neurotoxicity of Aβ, attenuating the apoptosis of brain neurons and improving the spatial learning and memory ability in AD models. Whether Trx-1 could inhibit pyroptosis in AD needs to be further investigated. METHODS AND RESULTS: In the present study, MTT assay was employed to detected the viability. Western blotting was employed to detect the protein levels. Enzyme linked immunosorbent assay was used to examine the intracellular and extracellular levels of IL-18 and IL-1β. Chronic Aβ25-35 treatment remarkedly compromised the viability of PC12 cells, increased the expression of NOD-like receptor pyrin domain containing 1 (NLRP-1), caspase-1 and gasdermin D (GSDMD), and promoted the extracellular release of interleukin (IL)-18 and IL-1β. Simultaneously, Aβ25-35 treatment also significantly reduced the intracellular protein levels of Trx-1. Pharmacological inhibition of Trx-1 activity further decreased the cell viability, activated the NLRP-1/caspase-1/GSDMD pyroptotic pathway, and exacerbated the extracellular release of IL-18 and IL-1β. CONCLUSIONS: These data suggest that Trx-1 may play a potential inhibitory effect on Aβ25-35-induced pyroptosis.
BACKGROUND: Alzheimer's disease (AD), the most common neurodegenerative disease, is charactered by these accepted pathological features, such as β-amyloid (Aβ) plaques outside the neurons and neurofibrillary tangles inside the neurons. In recent years, several studies have demonstrated that pyroptosis is associated with the development of AD process. However, whether Aβ25-35 induces pyroptosis is still unclear. Thioredoxin-1 (Trx-1), an intracellular multifunctional protein, showed neuroprotective roles by inhibiting the neurotoxicity of Aβ, attenuating the apoptosis of brain neurons and improving the spatial learning and memory ability in AD models. Whether Trx-1 could inhibit pyroptosis in AD needs to be further investigated. METHODS AND RESULTS: In the present study, MTT assay was employed to detected the viability. Western blotting was employed to detect the protein levels. Enzyme linked immunosorbent assay was used to examine the intracellular and extracellular levels of IL-18 and IL-1β. Chronic Aβ25-35 treatment remarkedly compromised the viability of PC12 cells, increased the expression of NOD-like receptor pyrin domain containing 1 (NLRP-1), caspase-1 and gasdermin D (GSDMD), and promoted the extracellular release of interleukin (IL)-18 and IL-1β. Simultaneously, Aβ25-35 treatment also significantly reduced the intracellular protein levels of Trx-1. Pharmacological inhibition of Trx-1 activity further decreased the cell viability, activated the NLRP-1/caspase-1/GSDMD pyroptotic pathway, and exacerbated the extracellular release of IL-18 and IL-1β. CONCLUSIONS: These data suggest that Trx-1 may play a potential inhibitory effect on Aβ25-35-induced pyroptosis.
Authors: Melissa K Edler; Chet C Sherwood; Richard S Meindl; William D Hopkins; John J Ely; Joseph M Erwin; Elliott J Mufson; Patrick R Hof; Mary Ann Raghanti Journal: Neurobiol Aging Date: 2017-08-01 Impact factor: 4.673
Authors: Theresa M Harrison; Richard Du; Giuliana Klencklen; Suzanne L Baker; William J Jagust Journal: Alzheimers Dement Date: 2020-12-15 Impact factor: 21.566