Article
Neurosciences
Lian Duan, Xueshen Qian, Qin Wang, Lan Huang, Song Ge
Summary: This study evaluated the impact of experimental periodontitis on cognitive function deficits in a rat model of streptozotocin-induced AD. The findings suggest that periodontitis may worsen cognitive deficits in an AD-like neurodegenerative context, possibly by impairing the insulin signaling pathway and stimulating gliosis and neuroinflammation.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Nanoscience & Nanotechnology
Smriti Gupta, Vishal Singh, Subramaniam Ganesh, Nitin K. Singhal, Rajat Sandhir
Summary: This study synthesized carboxylated graphene oxide nanosheets functionalized with PEG and PEI to attach GSK3 beta siRNA, resulting in reduced expression of APP and BACE1 genes. The knockdown of GSK3 beta also restored insulin signaling, AMPK and Mapk3 pathways, improving cellular energy homeostasis and neuronal functions. The nanoparticle-mediated targeting of GSK3 beta appears to be a promising strategy to reverse the pathology of sporadic Alzheimer's disease.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Nanoscience & Nanotechnology
Smriti Gupta, Vishal Singh, Subramaniam Ganesh, Nitin K. Singhal, Rajat Sandhir
Summary: Sporadic Alzheimer's disease (sAD) is a progressive neurodegenerative disorder associated with dysfunctional insulin signaling and energy metabolism. Experimental evidence suggests that siRNA targeting the gene GSK3 beta can reduce protein misfolding, improve cognitive function, and promote neuronal health.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Pharmacology & Pharmacy
Mohamed A. Salem, Barbara Budzynska, Joanna Kowalczyk, Nesrine S. El Sayed, Suzan M. Mansour
Summary: Tadalafil and bergapten exhibit neuroprotective effects in sporadic Alzheimer's disease models, enhancing cognitive function, preserving neuronal integrity, and reducing neuroinflammation through modulation of multiple signaling pathways and targets.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Anna Mietelska-Porowska, Justyna Domanska, Andrew Want, Angelika Wieckowska-Gacek, Dominik Chutoranski, Maciej Koperski, Urszula Wojda
Summary: Long-term consumption of Western diet may lead to insulin resistance and contribute to the development of Alzheimer's disease, with the entorhinal cortex being more sensitive to impaired brain insulin signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Geriatrics & Gerontology
Ningtian Ma, Yuyang Liang, Lingyun Yue, Pu Liu, Yuxia Xu, Cuiqing Zhu
Summary: This study investigated the effects of Tau overexpression and Tau phosphorylation on the insulin signaling pathway (ISP) in Alzheimer's disease (AD). The results showed that Tau overexpression upregulated the basal activity of elements in the ISP, but suppressed the insulin-induced activation of the pathway. This dysfunction of the ISP was more pronounced in cells overexpressing phosphorylated Tau. The study also found that the effects of lonafarnib, an anti-aging drug, on the ISP differed between cells overexpressing wild-type Tau and phosphorylated Tau, suggesting that Tau phosphorylation mediates additional effects on the pathway. These findings provide insights into the link between abnormal Tau expression and phosphorylation and ISP dysfunction in AD.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Plant Sciences
Panwen Liu, Chenkang Wang, Wenhui Chen, Yu Kang, Weiwei Liu, Zhiyue Qiu, Toshihiko Hayashi, Kazunori Mizuno, Shunji Hattori, Hitomi Fujisaki, Takashi Ikejima
Summary: Silibinin, a natural flavonoid from Silybum marianum seeds, has neuroprotective effects on sporadic Alzheimer's disease models. It exerts its effects by inhibiting over-activation of N-methyl-D-aspartate receptors (NMDARs).
Article
Biochemistry & Molecular Biology
Alaa Sirwi, Nesrine S. El Sayed, Hossam M. Abdallah, Sabrin R. M. Ibrahim, Gamal A. Mohamed, Ali M. El-Halawany, Martin K. Safo, Nora O. Abdel Rasheed
Summary: This study investigated the neuroprotective effects of the methoxy flavonoid umuhengerin in an STZ-induced SAD mouse model, showing that umuhengerin attenuated neuroinflammation and oxidative stress, increased Nrf2 expression, and decreased NF-Kβp65 expression. These results suggest that umuhengerin may be a potential therapy for Alzheimer's disease.
Article
Medicine, Research & Experimental
Inci Kazkayasi, Gokcen Telli, Emirhan Nemutlu, Serdar Uma
Summary: This study found that intranasal metformin treatment can improve learning and memory functions in ICV-STZ-induced AD mice, by increasing insulin sensitivity.
Article
Multidisciplinary Sciences
Wenqiang Chen, Qian Huang, Ekaterina Katie Lazdon, Antonio Gomes, Marisa Wong, Emily Stephens, Tabitha Grace Royal, Dan Frenkel, Weikang Cai, C. Ronald Kahn
Summary: This study shows that brain insulin signaling controls peripheral energy metabolism and plays a key role in mood and cognition regulation. The research suggests that insulin signaling in astrocytes contributes to Alzheimer's disease pathology, highlighting the potential importance of targeting insulin signaling in astrocytes for therapeutic interventions in patients with both type 2 diabetes and Alzheimer's disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Pharmacology & Pharmacy
Nesrine S. El Sayed, Esraa A. Kandil, Mamdooh H. Ghoneum
Summary: The study evaluated the potential therapeutic effects of probiotics fermentation technology in Alzheimer's disease (AD), showing that PFT is similar to pioglitazone in treatment efficacy and can target multiple mechanisms involved in AD pathogenesis, making it a beneficial therapy for AD.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Lucas Zangerolamo, Jean F. Vettorazzi, Carina Solon, Gabriela A. Bronczek, Daiane F. Engel, Mirian A. Kurauti, Gabriela M. Soares, Karina S. Rodrigues, Licio A. Velloso, Antonio C. Boschero, Everardo M. Carneiro, Helena C. L. Barbosa
Summary: Tauroursodeoxycholic acid (TUDCA) showed improvements in glucose tolerance and insulin sensitivity, reduced blood glucose levels, increased islet mass and beta-cell area, and enhanced glucose-stimulated insulin secretion in Alzheimer's disease (AD) models. Additionally, TUDCA also reduced neuroinflammation, decreased protein content of amyloid oligomers, improved memory, and increased protein content of insulin receptor beta-subunit in the hippocampus.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Neurosciences
Devanshi Mishra, Ishitha Reddy, Chinmoy Sankar Dey
Summary: Overexpression of PKC alpha inhibits insulin signaling by disrupting IRS-1 and Akt phosphorylations in skeletal muscle. PKC alpha is not necessary for insulin-stimulated glucose transport in skeletal muscles. Controversial studies have reported opposite expression pattern of PKC alpha in insulin-resistant skeletal muscles. Our study demonstrates that PKC alpha inhibits insulin signaling in neuronal cells through IRS-Akt pathway and PP2A-dependent mechanism, and silencing of PKC alpha improves insulin sensitivity. PKC alpha regulates GSK3 isoforms differently in insulin-sensitive and insulin-resistant conditions. These findings provide insights into the role of PKC alpha in regulating insulin resistance and diabetes in neuronal cells.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Suelen Santos Alves, Jose Antonio Cortes de Oliveira, Willian Lazarini-Lopes, Gabriel Servilha-Menezes, Mariana Grigorio-de-Sant'Ana, Flavio Del Vecchio, Rodrigo Focosi Mazzei, Sebastiao Sousa Almeida, Rui Milton Patricio da Silva Junior, Norberto Garcia-Cairasco
Summary: This study investigates the effects of neuronal insulin resistance in the link between Alzheimer's disease (AD) and epilepsy using a streptozotocin (STZ) induced AD model in rats. The results suggest that STZ may facilitate seizure generation and propagation by impairing neuronal function, especially in regions expressing high levels of insulin receptors. Impaired insulin signaling might be one of the mechanisms underlying the bidirectional connection between AD and epilepsy.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Chemistry, Medicinal
Jiayuan Chen, Li Gao, Yao Zhang, Ya Su, Zheng Kong, Dongqing Wang, Ming Yan
Summary: Acteoside has been shown to improve glucose and energy metabolism in the brain, alleviating cognitive impairment induced by ICV-STZ. This study suggests that acteoside can ameliorate learning and memory deficits by triggering intracerebral metabolism.
PHYTOTHERAPY RESEARCH
(2021)
Article
Neurosciences
Yang He, Jun Tang, Meng Zhang, Junjie Ying, Dezhi Mu
Summary: This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.
Article
Neurosciences
Emily L. Isenstein, Edward G. Freedman, Jiayi Xu, Ian A. DeAndrea-Lazarus, John J. Foxe
Summary: This study evaluated electrophysiological discrimination of parametric somatosensory stimuli in healthy young adults to understand how the brain processes the duration of tactile information. The results showed that participants did not electrophysiologically discriminate between 100 and 115 ms, but they exhibited distinct electrophysiological responses when the deviant stimuli were 130, 145, and 160 ms. These findings contribute to a better understanding of tactile sensitivity in different clinical conditions.
Article
Neurosciences
Juliana R. Souza, Ludmila Lima-Silveira, Daniela Accorsi-Mendonca, Benedito H. Machado
Summary: This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.
Article
Neurosciences
Miki Hashizume, Rina Ito, Rie Suge, Yasushi Hojo, Gen Murakami, Takayuki Murakoshi
Summary: The basolateral amygdaloid complex (BLA) is closely involved in the formation of emotional memories, including both aversive memory and contextual fear memory. Acute sleep deprivation (SD) disrupts the acquisition of tone-associated fear memory in juvenile rats, but has no significant effect on contextual fear memory. Slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.
Article
Neurosciences
Qunxian Wang, Shipeng Guo, Dongjie Hu, Xiangjun Dong, Zijun Meng, Yanshuang Jiang, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.