Article
Biochemistry & Molecular Biology
Erica Caballero, Elena Hernando-Perez, Victor Tapias, Maria Calvo-Rodriguez, Carlos Villalobos, Lucia Nunez
Summary: The Aβ oligomers in Alzheimer's disease promote calcium influx by amyloid channels and NMDA receptors, leading to excitotoxicity and neuron degeneration.
Review
Chemistry, Medicinal
Weimin Qiu, Hui Liu, Yijun Liu, Xin Lu, Lei Wang, Yanyu Hu, Feng Feng, Qi Li, Haopeng Sun
Summary: Alzheimer's disease (AD) is a difficult to treat progressive neurodegenerative disease characterized by the accumulation of amyloid beta (A beta) plaques in the brain. A beta interacts with various receptors on the plasma membrane and mediates signaling pathways that contribute to the development of AD. Despite ongoing research, there are currently no effective medications for AD. This review discusses the importance of A beta in the pathogenesis of AD, recent progress in targeting A beta-related receptors and compounds, and the challenges and opportunities in developing effective therapies for AD.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Miguel A. Olivencia, Marta Villegas-Esguevillas, Maria Sancho, Bianca Barreira, Elena Paternoster, Rui Adao, Maria Jesus Larriba, Angel Cogolludo, Francisco Perez-Vizcaino
Summary: Recent evidence suggests that vitamin D is involved in the development of pulmonary arterial hypertension (PAH). This study analyzed the electrophysiological and contractile properties of pulmonary arteries (PAs) in vitamin D receptor knockout mice (Vdr(-)(/-)). The results show that while Vdr(-)(/-) mice did not develop pulmonary hypertension, there was increased response to a Kv7 activator in their resistance PAs. This suggests that although Vdr deficiency alone may not induce PAH, the contribution of Kv7 channel currents to PA tone is increased in Vdr(-/-) mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Eleni Fella, Revekka Papacharalambous, Demos Kynigopoulos, Maria Ioannou, Rita Derua, Christiana Christodoulou, Myrto Stylianou, Christos Karaiskos, Alexia Kagiava, Gerasimou Petroula, Chryso Pierides, Maria Kyriakou, Laura Koumas, Paul Costeas, Elena Panayiotou
Summary: Research has found that the modified C5a receptor agonist (EP67) can significantly reduce beta-amyloid deposition and gliosis, and improve cognitive impairment in advanced stages of Alzheimer's disease. Proteomic analysis suggests that these effects may be triggered by the upregulation of beta-adrenergic and GABAergic signaling.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Neurosciences
Gillian Bonvicini, Stina Syvanen, Ken G. G. Andersson, Merja Haaparanta-Solin, Francisco Lopez-Picon, Dag Sehlin
Summary: This study investigates the efficacy of using transferrin receptor (TfR) as a targeting strategy to transport amyloid-beta (Aβ) immunoPET ligands across the blood-brain barrier (BBB). The results indicate that the affinity to TfR affects the efficiency of crossing the BBB, and this method shows potential for imaging Aβ pathology in rats.
TRANSLATIONAL NEURODEGENERATION
(2022)
Article
Cell Biology
Rai-Hua Lai, Yueh-Ying Hsu, Feng-Shiun Shie, Che-Ching Huang, Mei-Hsin Chen, Jyh-Lyh Juang
Summary: Observational epidemiological studies have shown an association between vitamin D deficiency and Alzheimer's disease, with increased hippocampal VDR levels in AD despite decreased vitamin D levels. Mechanistic investigations revealed a non-genomic rewiring of VDR to p53, leading to increased neuronal autophagy and apoptosis in AD pathogenesis. Targeting the VDR/p53 pathway may offer potential treatment for AD.
Article
Clinical Neurology
C. Mallinckrodt, Y. Tian, P. S. Aisen, F. Barkhof, S. Cohen, G. Dent, O. Hansson, K. Harrison, T. Iwatsubo, C. J. Mummery, K. K. Muralidharan, I. Nestorov, L. Nisenbaum, R. Rajagovindan, C. von Hehn, C. H. van Dyck, B. Vellas, S. Wu, Y. Zhu, A. Sandrock, T. Chen, S. Budd Haeberlein
Summary: Post-hoc analyses of the EMERGE and ENGAGE studies showed that the outcomes in the high-dose group of ENGAGE were affected by an imbalance in a small number of rapidly progressing patients and lower exposure to the target dose. However, these factors were only present in early enrolled patients and did not affect later enrolled patients. Baseline characteristics and amyloid-related imaging abnormalities did not contribute to the difference in results between the high-dose arms.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2023)
Article
Neurosciences
Yizhi Song, Zunshu Du, Xinyue Chen, Wanning Zhang, Guitao Zhang, Hui Li, Lirong Chang, Yan Wu
Summary: The study demonstrated that activation of astrocytic NMDARs can mitigate A beta-induced loss of synaptic proteins by increasing NGF release, while blockade of astrocytic NMDARs inhibits A beta-induced compensatory protective NGF increase. This highlights the important role of NMDARs in neurodegenerative diseases.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Elena V. V. Mitroshina, Alexander M. M. Pakhomov, Mikhail I. I. Krivonosov, Roman S. S. Yarkov, Maria S. S. Gavrish, Alexey V. V. Shkirin, Mikhail V. V. Ivanchenko, Maria V. V. Vedunova
Summary: This study investigates the impact of astrocytes on the calcium activity of neuron-astroglia networks in Alzheimer's disease (AD) modeling. The researchers developed an algorithm to analyze the dynamic directed graphs of both astrocytic and neuronal networks, allowing them to identify functional relationships and characterize the spread of calcium signal. The study found that Alzheimer's astrocytes can alter the functional pattern of calcium activity in healthy nerve cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Rai-Hua Lai, Chih-Cheng Hsu, Ben-Hui Yu, Yu-Ru Lo, Yueh-Ying Hsu, Mei-Hsin Chen, Jyh-Lyh Juang
Summary: Vitamin D deficiency may not be the cause but a consequence of AD. Supplementation of vitamin D in AD mice and humans exacerbates AD and enhances the non-genomic VDR/p53 complex in the brain. Long-term use of vitamin D-3 supplements may increase the risk of dementia and mortality.
Article
Clinical Neurology
S. Budd Haeberlein, P. S. Aisen, F. Barkhof, S. Chalkias, T. Chen, S. Cohen, G. Dent, O. Hansson, K. Harrison, C. von Hehn, T. Iwatsubo, C. Mallinckrodt, C. J. Mummery, K. K. Muralidharan, I. Nestorov, L. Nisenbaum, R. Rajagovindan, L. Skordos, Y. Tian, C. H. van Dyck, B. Vellas, S. Wu, Y. Zhu, A. Sandrock
Summary: Aducanumab showed significant changes in early Alzheimer's disease patients in one trial, but did not meet primary or secondary endpoints in another study. Both trials demonstrated a dose- and time-dependent reduction in pathophysiological markers of Alzheimer's disease.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Tomohiro Saito, Masahide Mizobuchi, Mariko Sakai, Takehisa Kawata, Tetsuya Kitayama, Tadashi Kato, Taihei Suzuki, Hiroaki Ogata, Fumihiko Koiwa, Hirokazu Honda
Summary: This study investigated the effect of calcimimetic evocalcet (Evo) on the expression of parathyroid calcium-sensing receptor (CaSR) and vitamin D receptor (VDR). The results showed that Evo and cinacalcet (Cina) can increase the expression of CaSR and VDR in uremic rats with secondary hyperparathyroidism (SHPT). The upregulation of these receptors may provide better control of mineral and bone disorder markers.
Article
Biochemistry & Molecular Biology
Tomohiro Saito, Masahide Mizobuchi, Mariko Sakai, Takehisa Kawata, Tetsuya Kitayama, Tadashi Kato, Taihei Suzuki, Hiroaki Ogata, Fumihiko Koiwa, Hirokazu Honda
Summary: It has been found that the expression of calcium and vitamin D receptors is reduced during hemodialysis. However, treatment with calcimimetic evocalcet (Evo) can enhance the expression of these receptors in hemodialysis patients, which contributes to better control of mineral and bone disorder markers.
Article
Chemistry, Medicinal
Minkui Zhang, Li Tang, Liu Jiang, Jun Wei, Yongzhou Hu, Rong Sheng
Summary: The newly designed compounds showed excellent H-3 receptor antagonistic activities and potent self-induced A beta aggregation inhibitory activities in vitro experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Clinical Neurology
Shang Wang, Taiyang Zhu, Wanyan Ni, Chao Zhou, Hui Zhou, Li Lin, Yuting Hu, Xiaoyu Sun, Jingjing Han, Yan Zhou, Guoliang Jin, Jie Zu, Hongjuan Shi, Xingxing Yang, Zuohui Zhang, Fang Hua
Summary: This study investigates the role of early activation of Toll-like receptor 3 (TLR3) in the pathophysiological process of Alzheimer's disease (AD). The results showed that the early activation of TLR3 attenuated neuronal loss and neurobehavioral dysfunction in a mouse model of AD. This could be attributed to its role in A beta clearance, the inhibition of glial cells, and the regulation of neuroinflammation in the hippocampus.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Neurosciences
Hande Yuceer, Duygu Gezen Ak, Gulcin Benbir Senel, Erdinc Dursun, Vuslat Yilmaz, Derya Karadeniz, Erdem Tuzun, Cem Ismail Kucukali
Summary: This study found that the activation of the classical pathway of complement is significant in narcolepsy, suggesting the involvement of immune mechanisms in its pathogenesis. The levels of complement factors and degradation products may serve as biomarkers for predicting the clinical severity of narcolepsy. Further investigation is needed to understand the role of autoantibodies in altering complement levels.
ACTA NEUROPSYCHIATRICA
(2022)
Article
Nutrition & Dietetics
William B. Grant, Fatme Al Anouti, Barbara J. Boucher, Erdinc Dursun, Duygu Gezen-Ak, Edward B. Jude, Tatiana Karonova, Pawel Pludowski
Summary: Vitamin D-3 has important health benefits, but there is a lack of awareness among healthcare professionals and the general public, leading to suboptimal levels of serum 25-hydroxyvitamin D in most of the world's population. High-quality studies show that vitamin D may reduce the risk of cardiovascular disease, cancer, etc., but randomized controlled trials in vitamin D research have flaws.
Article
Nutrition & Dietetics
Spyridon N. Karras, Erdinc Dursun, Merve Alaylioglu, Duygu Gezen-Ak, Fatme Al Anouti, Stefan Pilz, Pawel Pludowski, Edward Jude, Kalliopi Kotsa
Summary: Dysregulation of vitamin D-binding protein has been associated with various pregnancy complications. The effects of VDBP polymorphisms on adipokine profiles in mothers and neonates have not been fully investigated. This study found that VDBP polymorphisms had minimal impact on adiponectin, irisin, and VDBP concentrations at birth under different vitamin D status cut-offs.
Article
Clinical Neurology
Cem Ismail Kucukali, Busra Sengul, Duygu Gezen-Ak, Erdinc Dursun, Ece Erdag, Gurler Akpinar, Murat Kasap, Zerrin Karaaslan, Nermin Gorkem Sirin, Pinar Tekturk, Betul Baykan, Erdem Tuzun
Summary: A novel neuronal surface antibody to Kv5.1 was identified in patients with treatment-resistant epilepsy of unknown cause, suggesting a potential autoimmune etiology that requires further investigation.
Article
Pharmacology & Pharmacy
Burak Onal, Merve Alaylioglu, Erdinc Dursun, Duygu Gezen-Ak
Summary: In a cell line model of inflammation, vitamin D was found to decrease the expression of pro-atherosclerotic cytokines and increase the expression of anti-atherosclerotic cytokines, potentially reducing cardiovascular risks. Further verification through in vivo studies is needed.
TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Duygu Gezen-Ak, Zuhal Yurttas, Tugay Camoglu, Erdinc Dursun
Summary: In this review, we summarized clues of possible interactions between A beta and alpha-syn with mitochondria.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Nutrition & Dietetics
Spyridon N. Karras, Erdinc Dursun, Merve Alaylioglu, Duygu Gezen-Ak, Stefan Pilz, Cedric Annweiler, Fatme Al Anouti
Summary: This study aimed to evaluate the combined effect of maternal and neonatal VDBP polymorphism heterogeneity in conjunction with different maternal and neonatal 25(OH)D cutoffs on neonatal anthropometric profile at birth. The findings suggest a potential role for neonatal VDBP genotypes rs2298850 and rs4588, in conjunction with specific neonatal 25(OH)D cutoffs, in affecting neonatal growth and development. However, no significant effects were observed for maternal VDBP polymorphisms or maternal 25(OH)D concentrations at birth on neonatal anthropometry.
Article
Medicine, General & Internal
Handenur Goktan, Rahiye Dilhan Kuru, Sukriye Yilmaz, Merve Alaylioglu, Erdinc Dursun, Duygu Gezen Ak, Ayse Salihoglu, Ayhan Deviren
Summary: This study compared the effects of miRNA-210 and BCL-2 expressions on the prognosis of AML and their relationship with cytogenetic abnormalities. The results showed that increased levels of BCL-2 and miR-210 may have negative effects on the prognosis of the disease.
Article
Biochemistry & Molecular Biology
Duygu Gezen-Ak, Merve Alaylioglu, Zuhal Yurttas, Tugay Camoglu, Busra Sengul, Cihan Islerc, Umit Yasar Kina, Ebru Keskin, Irem Lutfiye Atasoy, Ali Metin Kafardar, Mustafa Uzan, Cedric Annweiler, Erdinc Dursun
Summary: In this study, it was found that Vitamin D receptor (VDR) may function as a mitochondrial transcription factor and regulate the transcription of mitochondrial DNA (mtDNA). The research also revealed the interaction between VDR and mitochondrial transcription factor A (TFAM), suggesting their joint involvement in the regulation of mitochondrial function. These findings not only uncover a novel role of VDR, but also highlight its indispensability for energy-demanding cells.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Endocrinology & Metabolism
C. Sulu, G. B. Senel, O. Koca, M. Alaylioglu, A. N. Demir, E. Durcan, D. G. Ak, E. Dursun, D. Konukoglu, H. M. Ozkaya, D. Karadeniz, P. Kadioglu
Summary: This study aimed to evaluate the sleep architecture of patients with Cushing's disease (CD) and investigate the role of agouti-related peptide (AgRP) and/or leptin in sleep alterations in patients with active CD. Polysomnography was performed on 26 patients with active CD and compared with age and sex-matched control subjects. The results showed that patients with CD had reduced sleep efficiency and increased wake after sleep onset, and their serum levels of AgRP and leptin were elevated. These findings suggest that CD is associated with impaired sleep efficiency and continuity, which may be influenced by elevated levels of AgRP and leptin.
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
(2023)
Article
Clinical Neurology
Zerrin Karaaslan, Busra Sengul-Yediel, Hande Yuceer-Korkmaz, Elif Sanlia, Duygu Gezen-Ak, Erdinc Dursun, Ozlem Timirci-Kahraman, Ahmet Tarik Baykal, Vuslat Yilmaz, Recai Turkoglu, Murat Kurtuncu, Tuncay Gunduz, Yasemin Gursoy-Ozdemir, Erdem Tuzun, Cem Ismail Kucukali
Summary: This study identified CLIC1-antibody in patients with multiple sclerosis (MS) and relapsing inflammatory optic neuritis (RION) for the first time, confirming anti-astrocytic autoimmunity in chronic inflammatory demyelinating disorders (CIDD). CLIC1-antibody may potentially serve as a diagnostic biomarker to differentiate between MS and NMOSD.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2023)
Article
Pharmacology & Pharmacy
B. Onal, M. Alaylioglu, G. Yenmis, A. S. Dogan, E. Dursun, D. Gezen-Ak, M. Ugurlucan
Summary: This study compared the efficacy of atorvastatin and pitavastatin in an inflammation model. The results showed that pitavastatin had superior inhibitory effects on certain pro-inflammatory cytokines compared to atorvastatin. This suggests that pitavastatin may be more suitable for controlling cardiovascular diseases caused by atherosclerosis.
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
(2022)