Review
Endocrinology & Metabolism
Yanjun Guo, Qinqiu Wang, Shenghui Chen, Chengfu Xu
Summary: This article summarizes the regulatory effects of APP and its cleavage peptides on metabolism in the central nervous system and peripheral tissues, indicating that peptides generated by non-amyloidogenic processing can have positive effects on metabolism, while those produced by amyloidogenic processing may have negative impacts. Abnormal expression of APP is associated with metabolic diseases (such as diabetes, obesity, etc.) and cancer.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2021)
Article
Biochemistry & Molecular Biology
Xiaoling Liu, Yan Liu, Shangrong Ji
Summary: Alzheimer's disease is a common neurodegenerative disease that increases in prevalence with age. Studies suggest that abnormalities in the metabolism of APP are a major pathological feature of AD, with secretases playing a key role in APP processing. Research on secretases in the processing of APP could potentially lead to new directions for AD therapy.
Review
Geriatrics & Gerontology
Jiang Chen, Jun-Sheng Chen, Song Li, Fengning Zhang, Jie Deng, Ling-Hui Zeng, Jun Tan
Summary: Decades of research have shown that amyloid-beta (Aβ) plays an undeniable role in the development of Alzheimer's disease (AD). However, the focus on the pathological effects of Aβ may overshadow the significance of its metabolic precursor, amyloid precursor protein (APP), in the occurrence and progression of AD. This review explores the various roles of APP in AD, including its structure, functions, enzymatic processing, and potential therapeutic approaches to targeting APP to ameliorate AD pathologies and halt disease progression.
Article
Neurosciences
Sandra Schilling, Ajay Pradhan, Amelie Heesch, Andrea Helbig, Kaj Blennow, Christian Koch, Lea Bertgen, Edward H. Koo, Gunnar Brinkmalm, Henrik Zetterberg, Stefan Kins, Simone Eggert
Summary: This study compares the effects of different APP genetic mutations on their processing and pathogenic mechanisms in Alzheimer's disease. The results show significant differences in the underlying mechanisms for familial AD mutations located at the alpha-, beta-, and gamma-secretase cleavage sites. Different mutations have different effects on APP processing and the generation of A β peptides.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Kseniia S. Orobets, Andrey L. Karamyshev
Summary: Alzheimer's disease is a common neurodegenerative disorder associated with age or inherited mutations. It is characterized by severe dementia that affects memory, cognitive functions, and daily life. The disease is linked to the accumulation of cytotoxic amyloid beta and hyperphosphorylated tau protein, as well as other pathological features. Various treatment options, such as antibody-based therapy and stem cell transplantation, are being investigated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
George A. Pantelopulos, Daisuke Matsuoka, James M. Hutchison, Charles R. Sanders, Yuji Sugita, John E. Straub, D. Thirumalai
Summary: This study reveals that the C-terminal domain of amyloid precursor protein (APP-C99) has thousands of structural states. The C99 monomer tends to form 13-strands in its C-terminal extramembrane domain, and homodimerization of C99 reduces the number of states and stabilizes extramembrane a-helices. The study also shows that the extramembrane domain structure affects the homodimerization motif and modifies the TM domain conformations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Svetlana Sharifulina, Andrey Khaitin, Valeria Guzenko, Yuliya Kalyuzhnaya, Valentina Dzreyan, Alexandr Logvinov, Natalia Dobaeva, Yan Li, Lei Chen, Bin He, Svetlana Demyanenko
Summary: Our studies uncover changes in the expression of key components involved in amyloid precursor protein (APP) processing in neurons and astrocytes after photothrombotic stroke (PTS). We demonstrate an increase in N- and C-terminal fragments of APP in the cytoplasm of ischemic penumbra cells 24 hours after PTS, along with their co-immunoprecipitation with caveolin-1. The level of ADAM10 alpha-secretase decreases in the rat brain cortex on the first day after PTS. In astrocytes, but not in neurons, levels of gamma-secretase complex proteins presenilin-1 and nicastrin are elevated in the penumbra after PTS. These changes result in neuronal death and astrocyte activation during the early recovery period after PTS. Inhibiting caveolin-1 shifts APP processing towards Aβ synthesis, leading to astroglial activation. Inhibiting gamma-secretase down-regulates glial fibrillary acidic protein (GFAP) in astrocytes, prevents apoptosis in mouse cerebral cortex cells induced by PTS, and reduces the size of the infarcted area. Hence, novel gamma-secretase inhibitors hold promise as potential therapeutics for stroke treatment.
Article
Biochemistry & Molecular Biology
Rhett J. Britton, James M. Hutchison, Charles R. Sanders
Summary: In Alzheimer's disease (AD) research, the proteins of interest are amyloid precursor protein (APP) and tau, which play crucial roles in the disease mechanism. The relationship between A beta and tau pathologies remains unclear, with studies suggesting that A beta may induce or enhance tau protein formation in neurofibrillary tangles.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Neurosciences
Yi Li, Jin-zhao Wang, Yue-ming Deng, Kun Wang, Li Yang, Cheng Long
Summary: This study suggests that A beta PP modulates neuronal firing and oscillatory activity in the hippocampus, and Kv1.4 may be involved in mediating the modulation.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Raquel Coronel, Victoria Lopez-Alonso, Marta I. Gallego, Isabel Liste
Summary: This article investigates the biological role of APP in hNSCs cells, revealing its association with cell proliferation and cell fate specification.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Vladimir Rudajev, Jiri Novotny
Summary: This article discusses the relationship between cholesterol and the development of Alzheimer's disease, as well as the influence of cholesterol on the production of amyloid beta (Aβ).
CELL AND BIOSCIENCE
(2023)
Article
Neurosciences
Qing Xia, XinYu Yang, JiaBin Shi, ZiJie Liu, YaHui Peng, WenJing Wang, BoWen Li, Yu Zhao, JiaYing Xiao, Lei Huang, DaYong Wang, Xu Gao
Summary: Alzheimer's disease is a neurodegenerative disorder characterized by abnormal accumulation of amyloid beta peptides and Tau protein in the brain. Mutations in amyloid precursor protein gene can cause familial Alzheimer's disease, but the A673T mutation shows protective effects against it.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Neurosciences
Rebecca M. C. Gabriele, Emily Abel, Nick C. Fox, Selina Wray, Charles Arber
Summary: Amyloid precursor protein (APP) and its cleavage fragment Amyloid-beta (A beta) play crucial roles in Alzheimer's disease (AD). Genetic alterations that increase the overall dosage of APP or favor the generation of more aggregation-prone A beta species directly contribute to the disease. Lowering APP expression is an attractive approach for AD treatment and prevention. New technologies that reduce APP expression may offer disease modification and slow clinical progression.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Raquel Coronel, Adela Bernabeu-Zornoza, Charlotte Palmer, Rosa Gonzalez-Sastre, Andreea Rosca, Patricia Mateos-Martinez, Victoria Lopez-Alonso, Isabel Liste
Summary: This study investigates the effects of amyloid precursor protein (APP) overexpression on human neural stem cells (hNSCs) and identifies differentially expressed genes related to neuronal and glial differentiation processes, as well as signaling pathways such as Notch, Wnt, PI3K-AKT, and JAK-STAT.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Jinhu Kim, Seungjoon Kim, Hyeonho Kim, In-Wook Hwang, Sungwon Bae, Sudeep Karki, Dongwook Kim, Roberto Ogelman, Geul Bang, Jin Young Kim, Tommi Kajander, Ji Won Um, Won Chan Oh, Jaewon Ko
Summary: Balanced synaptic inhibition is crucial for brain function. MDGA1 suppresses synaptic inhibition in mammalian neurons by interacting with APP, affecting GABAergic synaptic transmission in hippocampal CA1 neurons. Down-regulation of APP specifically suppresses GABAergic transmission strength and inputs in presynaptic interneurons. Overexpression of MDGA1 impairs novel object recognition memory in mice.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Jaya Padmanabhan, Kristy R. Brown, Amelia Padilla, Michael L. Shelanski
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Cell Biology
Sergiy I. Borysov, Antoneta Granic, Jaya Padmanabhan, Claire E. Walczak, Huntington Potter
Article
Biochemical Research Methods
Dale Chaput, Lisa Hornbeck Kirouac, Harris Bell-Temin, Stanley M. Stevens, Jaya Padmanabhan
Article
Neurosciences
Tim D. Boyd, Steven P. Bennett, Takashi Mori, Nicholas Governatori, Melissa Runfeldt, Michelle Norden, Jaya Padmanabhan, Peter Neame, Inge Wefes, Juan Sanchez-Ramos, Gary W. Arendash, Huntington Potter
JOURNAL OF ALZHEIMERS DISEASE
(2010)
Article
Biochemistry & Molecular Biology
Neha Kabra Woods, Jaya Padmanabhan
JOURNAL OF BIOLOGICAL CHEMISTRY
(2013)
Article
Biochemical Research Methods
Steven P. Bennett, Tim D. Boyd, Michelle Norden, Jaya Padmanabhan, Peter Neame, Inge Wefes, Huntington Potter
JOURNAL OF NEUROSCIENCE METHODS
(2009)
Article
Cell Biology
Antoneta Granic, Jaya Padmanabhan, Michelle Norden, Huntington Potter
MOLECULAR BIOLOGY OF THE CELL
(2010)
Article
Neurosciences
Monique Judge, Lisa Hornbeck, Huntington Potter, Jaya Padmanabhan
MOLECULAR NEURODEGENERATION
(2011)
Article
Geriatrics & Gerontology
Debrah I. Boeras, Antoneta Granic, Jaya Padmanabhan, Nichole C. Crespo, Amyn A. Rojiani, Huntington Potter
NEUROBIOLOGY OF AGING
(2008)
Article
Geriatrics & Gerontology
Csilla Ari, Sergiy I. Borysov, Jiashin Wu, Jaya Padmanabhan, Huntington Potter
NEUROBIOLOGY OF AGING
(2014)
Article
Multidisciplinary Sciences
Jose F. Abisambra, Tina Fiorelli, Jaya Padmanabhan, Peter Neame, Inge Wefes, Huntington Potter
Article
Oncology
Namrata Bora-Singhal, Biswarup Saha, Durairaj Mohankumar, Jaya Padmanabhan, Domenico Coppola, Srikumar Chellappan
Summary: The transcriptional coactivator YAP1 is regulated by VHL and PHD2 under normoxic conditions, while its levels are elevated and associated with HIF1α under hypoxic conditions. YAP1 plays a significant role in angiogenesis by regulating multiple genes and interacting with HIF1α, contributing to the onset and progression of tumors.
CANCER RESEARCH COMMUNICATIONS
(2022)
Article
Neurosciences
Lisa Kirouac, Alexander J. Rajic, David H. Cribbs, Jaya Padmanabhan
Article
Developmental Biology
Jaya Padmanabhan, Kristy Brown, Michael L. Shelanski
DEVELOPMENTAL NEUROBIOLOGY
(2007)