Review
Clinical Neurology
Kasper P. Kepp, Nikolaos K. Robakis, Poul F. Hoilund-Carlsen, Stefano L. Sensi, Bryce Vissel
Summary: Results from recent clinical trials of anti-amyloid antibodies for Alzheimer's disease have challenged the amyloid cascade hypothesis and indicated a more complex etiology. The treatments have shown no or uncertain clinical effect on cognition, suggesting that amyloid may play a minor role in the disease. Multiple pathogenic factors may contribute to Alzheimer's disease, and evolving multi-factor disease models may lead to more effective treatment strategies.
Review
Biochemistry & Molecular Biology
Markku Kurkinen, Michal Fulek, Katarzyna Fulek, Jan Aleksander Beszlej, Donata Kurpas, Jerzy Leszek
Summary: Old age increases the risk of Alzheimer's disease (AD), which is the most common neurodegenerative disease, and it is estimated that there will be 150 million people with AD by 2050. However, reducing A beta peptide production and amyloid formation did not slow cognitive decline in AD patients, challenging the amyloid hypothesis. Other avenues in AD research, such as the presenilin hypothesis and the role of astrocytes and the glutamate transporter EAAT2, are being explored.
Article
Cell Biology
Xiao Lin, WeiKai Li, Guangheng Dong, Qiandong Wang, Hongqiang Sun, Jie Shi, Yong Fan, Peng Li, Lin Lu
Summary: Abnormal brain connectivity is increasingly recognized as an important factor in the pathophysiology of schizophrenia. Multimodal network analyses showed high discrimination accuracies in distinguishing schizophrenia patients and first-degree relatives from healthy controls. Dysfunction in the communication between basal ganglia, thalamus, and prefrontal cortex could serve as biomarkers for schizophrenia.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Geriatrics & Gerontology
Marta Zampino, Richard G. Spencer, Kenneth W. Fishbein, Eleanor M. Simonsick, Luigi Ferrucci
Summary: This study found that decreased mitochondrial oxidative capacity is associated with cardiovascular risk and a history of cardiovascular disease, possibly due to excessive production of oxidative species by dysfunctional mitochondria. Lower energy production may impair the function of the heart and vessels, leading to a vicious cycle in cardiovascular health.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2021)
Review
Neurosciences
Russell H. Swerdlow
Summary: Viable hypotheses about Alzheimer's disease must consider its age-dependence, commonality, association with specific biological factors, connection with various changes in the body, and systemic features. Mitochondria and factors influenced by mitochondria may link these different characteristics. The mitochondrial cascade hypothesis provides a straightforward explanation and accumulating data support its validity. While alternative hypotheses may also explain mitochondria-related phenomena, the primary mitochondrial cascade hypothesis will continue to evolve and attract interest.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Clinical Neurology
K. Avgerinos, R. J. Mullins, J. M. Egan, D. Kapogiannis
Summary: This study investigates the AD biomarker and cognitive effects of ketone monoester (KME) in humans for the first time. KME is safe, induces robust ketosis, and animal studies suggest that it can modify AD pathology. By researching KME in a population at risk for AD, the study aims to bridge the gap between pre-clinical evidence and the potential brain-metabolic, pro-cognitive, and anti-Alzheimer's effects in humans.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Ernesto Fedele
Summary: In the past 30 years, most efforts to treat Alzheimer's disease (AD) have focused on clearing the beta-amyloid peptide (A beta) from the brain. However, clinical trial results suggest that A beta plays a minor role in the pathogenesis of AD. Additionally, A beta has been found to have various physiological functions, including memory formation, indicating that the loss of A beta function may contribute to AD. It is believed that AD could be the result of multiple molecular dysfunctions, and therefore, solely targeting A beta may overlook other important factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Benjamin Matis Pizarro-Galleguillos, Liesa Kunert, Norbert Brueggemann, Jannik Prasuhn
Summary: This review emphasizes the biological rationale for studying the pathways of Parkinson's disease and discusses the application of various neuroimaging methods in patients, as well as the limitations and challenges that need to be overcome for successful implementation in clinical studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Thomas Payne, Toby Burgess, Stephen Bradley, Sarah Roscoe, Matilde Sassani, Mark J. Dunning, Dena Hernandez, Sonja Scholz, Alisdair McNeill, Rosie Taylor, Li Su, Iain Wilkinson, Thomas Jenkins, Heather Mortiboys, Oliver Bandmann
Summary: This study characterized bioenergetic dysfunction in Parkinson's disease using a multimodal approach, and found impaired mitophagy and mitochondrial uncoupling in patient-derived fibroblasts. The study also revealed abnormal phosphocreatine levels and implicated a link between impaired mitophagy and impaired striatal energy homeostasis in early Parkinson's disease.
Article
Multidisciplinary Sciences
Haidong Li, Xiuchao Zhao, Yujin Wang, Xin Lou, Shizhen Chen, He Deng, Lei Shi, Junshuai Xie, Dazhong Tang, Jianping Zhao, Louis-S Bouchard, Liming Xia, Xin Zhou
Summary: The recovery process of COVID-19 patients remains unclear, with some experiencing ongoing respiratory issues. Xe-129 MRI analysis reveals higher ventilation defects and longer gas-blood exchange time in COVID-19 patients, indicating lung function impairment during recovery.
Article
Geriatrics & Gerontology
Tong Wu, Ding Lin, Yaqian Cheng, Senze Jiang, Muhammad Waheed Riaz, Nina Fu, Chenhao Mou, Menglu Ye, Ying Zheng
Summary: The amyloid cascade hypothesis has been a key focus in Alzheimer's disease therapeutic research. This review discusses the current hypothesis and pathogenesis, as well as drug development strategies targeting different stages in this hypothesis. Strategies like immunotherapy have shown promising results in clinical trials, but success rates remain low. The review also highlights common problems in drug development and emphasizes the importance of multidisciplinary cooperation and a better understanding of the amyloid cascade hypothesis.
Article
Clinical Neurology
Johannes Levin, Jonathan Voglein, Yakeel T. Quiroz, Randall J. Bateman, Valentina Ghisays, Francisco Lopera, Eric McDade, Eric Reiman, Pierre N. Tariot, John C. Morris
Summary: The amyloid cascade hypothesis for Alzheimer's disease has faced challenges due to inconsistent clinical benefits of drugs targeting amyloid beta peptide. It is important to conduct intervention studies in cognitively unimpaired individuals at risk for dementia to further evaluate the hypothesis.
ALZHEIMERS & DEMENTIA
(2022)
Review
Chemistry, Multidisciplinary
Florence Franconi, Laurent Lemaire, Jean-Christophe Gimel, Samuel Bonnet, Patrick Saulnier
Summary: NMR-based diffusion methods are valuable tools for nanomedicine characterization and understanding interactions with the biological environment. They provide insights into diffusion phenomena and measurement of self-diffusion and mutual diffusion coefficients. NMR diffusometry spectroscopic and imaging methods have broad applications in nanomedicine, aiding in elucidating important issues.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Biochemistry & Molecular Biology
Ruiqing Ni
Summary: Amyloid-beta (A beta) is crucial in the pathogenesis of Alzheimer's disease, with aberrant accumulation leading to neuroinflammation, cerebrovascular alterations, and cognitive impairments. High-field MRI technology has enabled non-invasive visualization of A beta-related alterations in animal models, offering translational value for clinical MRI applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Benjamin Matis Pizarro-Galleguillos, Liesa Kunert, Norbert Brueggemann, Jannik Prasuhn
Summary: There is a need for disease-modifying therapies for neurodegenerative diseases such as Parkinson's disease (PD). However, clinical trial designs for these disorders face challenges in assessing the neuroprotective properties of potential drugs due to unknown individual disease mechanisms. Neuroimaging methods can provide insights into disease mechanisms, help with patient stratification, and map treatment responses. This review highlights the role of neuroinflammation and mitochondrial dysfunction in PD, discusses different neuroimaging modalities and their challenges, and explores opportunities for future clinical trials.
Article
Endocrinology & Metabolism
Emilie Steinbach, Davide Masi, Agnes Ribeiro, Patricia Serradas, Tiphaine Le Roy, Karine Clement
Summary: The study of the gut microbiome is crucial for understanding and treating metabolic diseases. While research on the fecal microbiome has provided valuable insights, relying solely on this may not be enough to draw comprehensive conclusions. The microbiome in the proximal part of the small intestine may play a significant role in metabolic regulation, but further exploration is needed due to limited accessibility.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2024)
Article
Endocrinology & Metabolism
Evangelia Chavdoula, Vollter Anastas, Alessandro La Ferlita, Julian Aldana, Giuseppe Carota, Mariarita Spampinato, Burak Soysal, Ilaria Cosentini, Sameer Parashar, Anuvrat Sircar, Giovanni Nigita, Lalit Sehgal, Michael A. Freitas, Philip N. Tsichlis
Summary: This study reveals the important role of KDM2B in triple-negative breast cancer (TNBC). KDM2B affects cellular resistance to oxidative stress by regulating a network of genes and metabolic enzymes, in collaboration with ATF4 and MYC. Additionally, high expression of KDM2B is associated with poor prognosis in patients.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2024)
Article
Endocrinology & Metabolism
Joongmin Kim, Hyeongsoo Kim, Sang Hyun Park, Yura Kang, Kyungdo Han, Sang-Hak Lee
Summary: This study aimed to investigate the optimal LDL-C level after statin therapy in individuals with intermediate cardiovascular risk. The results showed that achieving LDL-C levels <120 mg/dL after statin therapy could lower the event risk.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2024)
Review
Endocrinology & Metabolism
Ze Chen, Li -Ping Xia, Lang Shen, Dan Xu, Yu Guo, Hui Wang
Summary: Accumulating evidence suggests that NAFLD has an intrauterine origin, with adverse prenatal environments and glucocorticoid exposure playing a crucial role in the developmental programming of fetal hepatic lipid metabolism. The offspring's glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis is programmed in utero, leading to postnatal catch-up growth and disrupted glucose and lipid metabolism, increasing susceptibility to NAFLD. Mismatch between intrauterine and postnatal environments can further disturb the programmed endocrine axes and accelerate the onset of NAFLD.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2024)
Article
Endocrinology & Metabolism
Fuwen Zuo, Youzhao Wang, Xinlei Xu, Ruihao Ding, Wei Tang, Yu Sun, Xiaojie Wang, Yan Zhang, Jichao Wu, Yusheng Xie, Min Liu, Ziying Wang, Fan Yi
Summary: This study investigates the role of CCDC92 in the pathogenesis of diabetic kidney disease (DKD). The expression of CCDC92 was found to increase in kidney biopsies from patients with DKD and was correlated with glomerular lipid accumulation. Animal studies further confirmed the induction of CCDC92 in the kidney, particularly in podocytes, and the podocyte-specific deletion of Ccdc92 ameliorated podocyte injury and lipid deposition. CCDC92 was shown to promote podocyte lipotoxicity through ABCA1 signaling-mediated lipid homeostasis. Therefore, CCDC92 may serve as a potential biomarker of podocyte injury in DKD and targeting CCDC92 could be an innovative therapeutic strategy for DKD patients.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2024)
Review
Endocrinology & Metabolism
Khanyisani Ziqubu, Phiwayinkosi Dludla, Sihle E. Mabhida, Babalwa U. Jack, Susanne Keipert, Martin Jastroch, Sithandiwe E. Mazibuko-Mbeje
Summary: The discovery and revival of brown adipose tissue (BAT) in adult humans have opened up new possibilities for treating obesity and metabolic diseases. BAT not only plays a role in generating heat, but also secretes signaling molecules known as batokines, which regulate overall metabolism. This review highlights the importance of BAT-derived metabolites in controlling thermogenesis, substrate metabolism, and other biological processes, as well as their potential to alleviate obesity and related metabolic complications.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2024)