Article
Biochemistry & Molecular Biology
Maria-Angeles Cortes-Gomez, Victor M. Barbera, Jordi Alom, Javier Saez-Valero, Maria-Salud Garcia-Ayllon
Summary: In Alzheimer's disease, the inactive and active forms of acetylcholinesterase (AChE) exhibit differences in their glycosylation pattern, particularly in the presence of terminal mannoses in the active forms. Sporadic AD patients have reduced binding to terminal mannoses compared to non-demented individuals, while familial AD patients with PSEN1 gene mutations have higher binding. Furthermore, presenilin-1 (PS1) modulates AChE trafficking and maturation in Golgi regions, promoting the presence of active forms in the cell membrane.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Gee Euhn Choi, Ji Yong Park, Mo Ran Park, Jee Hyeon Yoon, Ho Jae Han
Summary: The release of glucocorticoid induced by stress is an important factor in the formation of amyloid, which increases the levels of amyloid precursor protein (APP) and beta secretase 1 (BACE1). Glucocorticoid also contributes to the development of Alzheimer's disease (AD) by promoting the connection between the endoplasmic reticulum (ER) and mitochondria, where amyloid beta (Aβ) is processed due to its lipid raft-rich characteristics. However, the mechanism by which glucocorticoid enhances gamma-secretase activity in the mitochondrial-associated membrane of ER (MAM) and leads to the accumulation of mitochondrial Aβ remains unclear.
Article
Medicine, Research & Experimental
Jihoon Han, Heejin Park, Chinmoyee Maharana, A-Ryeong Gwon, Jinsu Park, Seung Hyun Baek, Han-Gyu Bae, Yoonsuk Cho, Hark Kyun Kim, Jae Hoon Sul, Jeongmi Lee, Eunae Kim, Junsik Kim, Yongeun Cho, Sunyoung Park, Leon F. Palomera, Thiruma Arumugam, Mark P. Mattson, Dong-Gyu Jo
Summary: The five FAD-linked PS1 mutations have been shown to have deleterious effects on mitochondrial functions in different ways. Each PS1 mutant affected mitochondrial morphology and function differently, with some inducing mitochondrial fragmentation while others increased MAMs formation and oxidative stress. These mutations compromised mitochondrial membrane potential and ATP production, which may contribute to an accelerated age of disease onset in individuals with mutant PS1.
Article
Biochemistry & Molecular Biology
Kyu-Hwan Shim, Min-Ju Kang, Heewon Bae, Danyeong Kim, Jiwon Park, Seong-Soo A. An, Da-Eun Jeong
Summary: A novel PSEN2 mutation was identified in a patient with early-onset Alzheimer's disease, which may promote the pathogenesis of the disease through altered phosphorylation of presenilin and APP processing. Further functional studies are needed to clarify the pathogenicity of the mutation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Xin Chen, Ana Joyce Munoz-Arellano, Dina Petranovic
Summary: UBB+1 accumulation is linked to UPS dysfunction and neurodegeneration, while low UBB+1 expression activates the autophagy pathway and reduces intracellular A beta toxicity.
Review
Cell Biology
Rupkatha Banerjee, Shermali Gunawardena
Summary: It has been 25 years since the discovery of phosphorylation in molecular motors, but the specific contribution of kinases to motor functions, particularly in vivo, and the evolutionary conservation of these processes, still remain largely unanswered. There is a critical need to understand how kinases regulate molecular motors due to their crucial role in intracellular processes and cell viability, as disruptions can lead to diseases such as cancer and neurodegeneration. This review focuses on the role of phosphorylation in controlling kinesin-1 motility and presents evidence for a novel regulatory mechanism involving the kinase glycogen synthase kinase 3 beta (GSK3 beta) and the scaffolding protein presenilin (PS).
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Geriatrics & Gerontology
Gustavo Lopez-Toledo, Maria-del-Carmen Silva-Lucero, Jorge Herrera-Diaz, David-Erasmo Garcia, Jose-Antonio Arias-Montano, Maria-del-Carmen Cardenas-Aguayo
Summary: Alzheimer's disease is a neurodegenerative disorder characterized by memory loss and decline in cognitive ability. This study found that skin fibroblasts from patients with familial Alzheimer's disease exhibited abnormalities in signaling pathways related to neurodegeneration, which may contribute to disease modeling and early biomarker identification.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Plant Sciences
Jikai Xu, Jingyu Liu, Qing Li, Guoxun Li, Guijie Zhang, Yan Mi, Ting Zhao, Danyang Mu, Dequan Wang, Kewu Zeng, Yue Hou
Summary: This study found that pterostilbene, a compound isolated from Chinese dragon's blood, can reduce inflammation in Alzheimer's disease (AD). The study demonstrated that pterostilbene can improve learning and memory abilities in AD transgenic mice and reduce microglial activation and A beta aggregation in their hippocampus. This is achieved by blocking the interaction of TLR4 and MD2 to suppress TLR4-mediated inflammation.
Article
Multidisciplinary Sciences
Pearl P. Y. Lie, Lang Yoo, Chris N. Goulbourne, Martin J. Berg, Philip Stavrides, Chunfeng Huo, Ju-Hyun Lee, Ralph A. Nixon
Summary: This study reveals the dysfunction and mistrafficking of organelles in autophagy- and endosomal-lysosomal pathways associated with neurodegenerative diseases. The researchers found that degradative organelles in axons are selectively vulnerable to local calcium dysregulation, which is greatly influenced by the activation of TRPML1 channels. The study also identified a mechanism involving calcium-mediated JNK activation and DIC1B serine-80 phosphorylation that contributes to neuritic dystrophy.
Article
Geriatrics & Gerontology
Yuan Gao, Yang Sun, Sadequl Islam, Tomohisa Nakamura, Taisuke Tomita, Kun Zou, Makoto Michikawa
Summary: Alzheimer's disease (AD) is associated with the accumulation of amyloid beta-protein 1-42 (A beta 42) in the brain. Angiotensin-converting enzyme (ACE) can convert neurotoxic A beta 42 to neuroprotective A beta 40 in a glycosylation-dependent manner. Mutations in the PSEN1 gene are the main cause of familial AD and lead to an increased A beta 42/40 ratio, but the mechanism behind this is still unclear.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Neurosciences
Ye-Ran Wang, Meng-Ting Wang, Xiao-Qin Zeng, Yu-Hui Liu, Yan-Jiang Wang
Summary: This study found lower plasma levels of NAbs-PS1 in AD patients, which were negatively associated with brain A beta load and positively associated with cognitive functions. Plasma NAbs-PS1 could be potential biomarkers for distinguishing AD patients from non-AD cognitive impairment subjects.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Cell Biology
Lucia Barazzuol, Domenico Cieri, Nicola Facchinello, Tito Cali, Philip Washbourne, Francesco Argenton, Paola Pizzo
Summary: This study generated a zebrafish line with a psen2 knockout, and found that the absence of the protein does not significantly affect Notch signaling, but leads to an exaggeration of locomotor response, a decrease in ER-mitochondria contacts, and an increase in basal autophagy. The protein also plays a role in mitochondrial axonal transport, and its downregulation reduces organelle flux in zebrafish sensory neurons. These findings highlight zebrafish as a valuable model organism for studying PS2 functions and testing potential therapies for Alzheimer's disease.
Article
Neurosciences
Masato Maesako, Mei C. Q. Houser, Yuliia Turchyna, Michael S. Wolfe, Oksana Berezovska
Summary: In this study, we used a novel imaging method to visualize the subcellular compartment where γ-secretase primarily cleaves C99 to generate Aβ in mouse cortical neurons. Our findings suggest that γ-secretase processes C99 mainly in low-pH compartments and Aβ is accumulated in the same subcellular loci. Additionally, we found a functional correlation between endo-lysosomal pH and cellular γ-secretase activity.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Eunju Im, Ying Jiang, Philip H. H. Stavrides, Sandipkumar Darji, Hediye Erdjument-Bromage, Thomas A. A. Neubert, Jun Yong Choi, Jerzy Wegiel, Ju-Hyun Lee, Ralph A. Nixon
Summary: The dysfunction of lysosomes is an early event in Alzheimer's disease (AD). A study reveals that the beta C-terminal fragment (beta CTF) of amyloid precursor protein (APP), which is linked to early-onset AD in Down syndrome (DS), disrupts lysosomal acidification by inhibiting the v-ATPase activity.
Review
Pharmacology & Pharmacy
Mohammad Rafi Khezri, Keyvan Yousefi, Negin Mahboubi, Darya Hodaei, Morteza Ghasemnejad-Berenji
Summary: Alzheimer's disease (AD) is a common neurodegenerative disorder worldwide, and its association with diseases like diabetes has been well-studied. Metformin, a medication commonly used for type 2 diabetes, has shown potential disease-modifying effects on various aspects of AD pathophysiology.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
J-S Seo, P. Zhong, A. Liu, Z. Yan, P. Greengard
MOLECULAR PSYCHIATRY
(2018)
Article
Medicine, General & Internal
Rury R. Holman, M. Angelyn Bethel, Robert J. Mentz, Vivian P. Thompson, Yuliya Lokhnygina, John B. Buse, Juliana C. Chan, Jasmine Choi, Stephanie M. Gustavson, Nayyar Iqbal, Aldo P. Maggioni, Steven P. Marso, Peter Ohman, Neha J. Pagidipati, Neil Poulter, Ambady Ramachandran, Bernard Zinman, Adrian F. Hernandez
NEW ENGLAND JOURNAL OF MEDICINE
(2017)
Article
Multidisciplinary Sciences
William J. Netzer, Karima Bettayeb, Subhash C. Sinha, Marc Flajolet, Paul Greengard, Victor Bustos
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Multidisciplinary Sciences
Victor Bustos, Maria V. Pulina, Ashley Bispo, Alison Lam, Marc Flajolet, Fred S. Gorelick, Paul Greengard
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Editorial Material
Gastroenterology & Hepatology
M. Brian Fennerty, Kenneth McQuaid, Fred Gorelick
Article
Gastroenterology & Hepatology
Gyorgy Biczo, Eszter T. Vegh, Natalia Shalbueva, Olga A. Mareninova, Jason Elperin, Ethan Lotshaw, Sophie Gretler, Aurelia Lugea, Sudarshan R. Malla, David Dawson, Piotr Ruchala, Julian Whitelegge, Samuel W. French, Li Wen, Sohail Z. Husain, Fred S. Gorelick, Peter Hegyi, Zoltan Rakonczay, Ilya Gukovsky, Anna S. Gukovskaya
Article
Multidisciplinary Sciences
A. A. Alahmari, B. Sreekumar, V. Patel, M. Ashat, M. Alexandre, A. K. Uduman, E. Akinbiyi, A. Ceplenski, C. A. Shugrue, T. R. Kolodecik, N. Tashkandi, S. W. Messenger, G. E. Groblewski, F. S. Gorelick, E. C. Thrower
Article
Biochemistry & Molecular Biology
Mingming Zhou, Jodi Gresack, Jia Cheng, Kunihiro Uryu, Lars Brichta, Paul Greengard, Marc Flajolet
MOLECULAR PSYCHIATRY
(2020)
Article
Multidisciplinary Sciences
Eitan Wong, George P. Liao, Jerry C. Chang, Peng Xu, Yue-Ming Li, Paul Greengard
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Biochemistry & Molecular Biology
Sudarshan R. Malla, Burkhard Krueger, Thomas Wartmann, Matthias Sendler, Ujjwal M. Mahajan, F. Ulrich Weiss, Franziska G. Thiel, Carina De Boni, Fred S. Gorelick, Walter Halangk, Ali A. Aghdassi, Thomas Reinheckel, Anna S. Gukovskaya, Markus M. Lerch, Julia Mayerle
CELLULAR AND MOLECULAR LIFE SCIENCES
(2020)
Article
Genetics & Heredity
Fatemehsadat Esteghamat, James S. Broughton, Emily Smith, Rebecca Cardone, Tarun Tyagi, Mateus Guerra, Andras Szabo, Nelson Ugwu, Mitra Mani, Bani Azari, Gerald Kayingo, Sunny Chung, Mohsen Fathzadeh, Ephraim Weiss, Jeffrey Bender, Shrikant Mane, Richard P. Lifton, Adebowale Adeniran, Michael H. Nathanson, Fred S. Gorelick, John Hwa, Miklos Sahin-Toth, Renata Belfort-DeAguiar, Richard G. Kibbey, Arya Mani
Review
Gastroenterology & Hepatology
Jami L. Saloman, Kathryn M. Albers, Zobeida Cruz-Monserrate, Brian M. Davis, Mouad Edderkaoui, Guido Eibl, Ariel Y. Epouhe, Jeremy Y. Gedeon, Fred S. Gorelick, Paul J. Grippo, Guy E. Groblewski, Sohail Z. Husain, Keane K. Y. Lai, Stephen J. Pandol, Aliye Uc, Li Wen, David C. Whitcomb
Article
Biochemistry & Molecular Biology
Remzi Karayol, Lucian Medrihan, Jennifer L. Warner-Schmidt, Ben W. Fait, Meghana N. Rao, Eva B. Holzner, Paul Greengard, Nathaniel Heintz, Eric F. Schmidt
Summary: The study demonstrates that the loss of functional 5-HT4R specifically from excitatory neurons of the hippocampus leads to AD-like behavioral responses and an increase in anxiety levels, accompanied by an increase in the number of neurons in different regions of the hippocampus. This research highlights the importance of cell type-based approaches in elucidating the complex actions of neuromodulatory systems on neural circuits.
MOLECULAR PSYCHIATRY
(2021)
Article
Urology & Nephrology
J. Chang, X. Guo, V Rao, E. S. Gromisch, S. Chung, H. M. Kluger, C. Cha, F. Gorelick, J. Testani, R. Safirstein, S. Crowley, A. J. Peixoto, G. Desir
KIDNEY INTERNATIONAL REPORTS
(2020)
Article
Gastroenterology & Hepatology
Mark E. Lowe, Dana K. Andersen, Richard M. Caprioli, Jyoti Choudhary, Zobeida Cruz-Monserrate, Anil K. Dasyam, Christopher E. Forsmark, Fred S. Gorelick, Joe W. Gray, Mark Haupt, Kimberly A. Kelly, Kenneth P. Olive, Sylvia K. Plevritis, Noa Rappaport, Holger R. Roth, Hanno Steen, S. Joshua Swamidass, Temel Tirkes, Aliye Uc, Kirill Veselkov, David C. Whitcomb, Aida Habtezion