Review
Biochemistry & Molecular Biology
Jannigje Rachel Kok, Nelma M. Palminha, Cleide Dos Santos Souza, Sherif F. El-Khamisy, Laura Ferraiuolo
Summary: Increasing evidence supports the involvement of DNA damage in various neurodegenerative diseases, including ALS. DNA damage in ALS may vary between genetic subgroups, particularly with repeat expansion in the C9ORF72 gene. Several genes associated with ALS, such as TARDBP, FUS, NEK1, SQSTM1 and SETX, may contribute to neuronal death by affecting DNA repair and the DNA damage response.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Endocrinology & Metabolism
Patrycja Mulica, Anne Gruenewald, Sandro L. Pereira
Summary: Declining brain energetics play a role in aging and neurodegenerative diseases like Alzheimer's and Parkinson's. Recent evidence suggests that astrocytes, key in supporting neuronal function, may also contribute to the development of these diseases. Understanding the metabolic interactions between astrocytes and neurons, particularly regarding mitochondria, has therapeutic potential in addressing neurodegenerative disorders.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Immunology
Arthur A. Vandenbark, Halina Offner, Szymon Matejuk, Agata Matejuk
Summary: The brain is the body's most unique and complex organ, and neurological disorders are the result of a failure of the nervous system multifaceted cellular networks. Microglia and astrocytes play important roles in neurological disorders, and understanding their contributions can lead to advances in related fields.
JOURNAL OF NEUROINFLAMMATION
(2021)
Review
Biochemistry & Molecular Biology
Zhong-Xuan Wang, Yao-Lin Li, Jia-Li Pu, Bao-Rong Zhang
Summary: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, and the role of DNA damage and repair deficiency in its pathogenesis has been increasingly recognized. This review provides an overview of the current understanding of DNA damage and repair in PD, including the evidence and causes of DNA damage, the potential pathways linking DNA damage to neurotoxicity, and possible interventions targeting DNA damage and repair. Future research should focus on addressing key issues to further elucidate the role of DNA damage in PD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Pablo Diaz-Amarilla, Florencia Arredondo, Rosina Dapueto, Victoria Boix, Diego Carvalho, Maria Daniela Santi, Elena Vasilskis, Raquel Mesquita-Ribeiro, Federico Dajas-Bailador, Juan Andres Abin-Carriquiry, Henry Engler, Eduardo Savio
Summary: Alzheimer's disease is primarily a neuronal pathology, but growing evidence suggests the involvement of glial cells, particularly astrocytes, in the disease progression. Old astrocytes in the 3xTg-AD mouse model exhibited altered gene expression and high proliferation rate compared to controls. These astrocytes were neurotoxic to primary neuronal cultures, activating apoptosis pathways. Understanding the role of these astrocytes can provide insights into the disease mechanisms and potential therapeutic opportunities.
NEUROCHEMISTRY INTERNATIONAL
(2022)
Article
Neurosciences
Sanming Li, Ethan R. Roy, Yanyu Wang, Trent Watkins, Wei Cao
Summary: Alzheimer's disease is a neurodegenerative disorder, and tau aggregation is closely linked to its clinical progression. This study overexpressed human tau in primary mouse neurons and observed significant axonal degeneration and cell death, providing convincing evidence for the association between tau-induced neurodegeneration and AD.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Andrea Vergallo, Pablo Lemercier, Enrica Cavedo, Simone Lista, Eugeen Vanmechelen, Ann De Vos, Henrik Zetterberg, Kaj Blennow, Marie-Odile Habert, Marie-Claude Potier, Bruno Dubois, Stefan Teipel, Harald Hampel
Summary: The study identified a positive correlation between plasma BACE1 protein concentrations and AD biomarkers of neurodegeneration, suggesting a potential role of BACE1 in Alzheimer's disease progression.
ALZHEIMERS & DEMENTIA
(2021)
Article
Biochemistry & Molecular Biology
Owen Davis Sanders, Lekshmy Rajagopal, Jayalekshmi Archa Rajagopal
Summary: The amyloid-beta oligomer hypothesis of Alzheimer's disease remains dominant in the field, but clinical trial evidence does not strongly support it. To rescue the hypothesis, researchers propose a new ad-hoc hypothesis suggesting that the vulnerable hippocampus may produce A beta peptides even in healthy aging individuals, and DNA damage, pathogens, and metal ions may drive A beta peptide aggregation and contribute to neurodegeneration in AD.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Gwyneth Welch, Li-Huei Tsai
Summary: Neurons are highly susceptible to DNA damage, and deficient DNA damage repair is the underlying cause of neurological disorders. DNA damage may play a central role in neuroinflammation associated with neurodegenerative diseases.
Article
Multidisciplinary Sciences
Gihan P. Ruwanpathirana, Robert C. Williams, Colin L. Masters, Christopher C. Rowe, Leigh A. Johnston, Catherine E. Davey
Summary: The molecular mechanism of intracellular tau accumulation caused by extracellular A beta-amyloid (A beta) in Alzheimer's disease is not well understood. This study used a convolutional neural network (CNN) to analyze the association between A beta and tau, revealing new associations. The CNN accurately predicted the relationship between A beta and tau.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Rawan Tarawneh
Summary: Alzheimer's disease (AD) models propose that abnormal protein aggregation is the primary event in AD, but recent evidence indicates that reduced blood flow due to capillary loss and endothelial dysfunction may be the early and primary events in AD pathogenesis. These vascular factors may precede amyloid and tau aggregation and contribute to neuronal and synaptic injury. Clinical studies have shown that endothelial dysfunction is closely related to cognitive outcomes in AD, suggesting that promoting endothelial repair in early AD may be a potential therapeutic strategy to slow disease progression. This review examines evidence from various studies supporting the vascular hypothesis of AD and emphasizes the need for further investigations into its role in the disease.
Article
Neurosciences
Nidheesh Thadathil, David F. Delotterie, Jianfeng Xiao, Roderick Hori, Michael P. McDonald, Mohammad Moshahid Khan
Summary: Alzheimer's disease (AD) is characterized by progressive neurodegeneration with accumulation of DNA double-strand breaks (DSBs) playing an important role in its pathogenesis. Studies have shown increased DNA DSB accumulation and reduced repair function in the hippocampus of AD brains compared to non-AD brains. Additionally, altered levels of DNA repair proteins were observed in AD mouse models and cellular models, highlighting the potential influence of DNA DSB and repair proteins in the pathway toward neural damage and memory loss in AD.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Cell Biology
Geraldine Zimmer-Bensch, Hans Zempel
Summary: Tauopathies, including Alzheimer's Disease, are common neurological disorders that primarily affect the aging population, but can also impact children and young adults. Characterized by cognitive dysfunction and movement abnormalities, these diseases can lead to severe neurological deficits and premature death. Genetic and epigenetic factors play a role in the etiology of tauopathies, with potential diagnostic and therapeutic implications.
Article
Neurosciences
Jenny Lange, Olivia Gillham, Michael Flower, Heather Ging, Simon Eaton, Sneha Kapadia, Andreas Neueder, Michael R. Duchen, Patrizia Ferretti, Sarah J. Tabrizi
Summary: Huntington's Disease is a neurodegenerative disease caused by a genetic mutation. Astrocyte dysfunction, specifically changes in gene expression and metabolic activity, plays a role in the pathogenesis of the disease. Additionally, all Huntington's Disease astrocytes exhibit increased DNA damage and a DNA damage response, suggesting a potential mechanism for their dysfunction.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Neurosciences
Asha Sinha, Sachin Katyal, Tiina M. Kauppinen
Summary: This study demonstrates the differential effects of various PARP inhibitors on cell viability and DNA integrity, with talazoparib and olaparib causing DNA damage and promoting PARP trapping onto DNA, while PJ34 and minocycline do not. The findings suggest the importance of selective use of PARP inhibitors in the treatment of neurodegenerative disorders, where inhibition of PARP enzymatic activity must occur without deleteriously trapping PARP onto DNA.
Letter
Clinical Neurology
P. F. Hoilund-Carlsen, A. Alavi, G. Perry, J. R. Barrio
AMERICAN JOURNAL OF NEURORADIOLOGY
(2023)
Editorial Material
Neurosciences
George Perry
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Biographical-Item
Neurosciences
George Perry
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Plant Sciences
Rajeev K. Singla, Ronita De, Thomas Efferth, Bruno Mezzetti, Md Sahab Uddin, Sanusi, Fidele Ntie-Kang, Dongdong Wang, Fabien Schultz, Kiran R. Kharat, Hari Prasad Devkota, Maurizio Battino, Daniel Sur, Ronan Lordan, Sourav S. Patnaik, Christos Tsagkaris, Chandragiri Siva Sai, Surya Kant Tripathi, Mihnea-Alexandru Gaman, Mosa E. O. Ahmed, Elena Gonzalez-Burgos, Smith B. Babiaka, Shravan Kumar Paswan, Joy Ifunanya Odimegwu, Faizan Akram, Jesus Simal-Gandara, Magali S. Urquiza, Aleksei Tikhonov, Himel Mondal, Shailja Singla, Sara Di Lonardo, Eoghan J. Mulholland, Merisa Cenanovic, Abdulkadir Yusif Maigoro, Francesca Giampieri, Soojin Lee, Nikolay T. Tzvetkov, Anna Maria Louka, Pritt Verma, Hitesh Chopra, Scarlett Perez Olea, Johra Khan, Jose M. Alvarez Suarez, Xiaonan Zheng, Michal Tomczyk, Manoj Kumar Sabnani, Christhian Delfino Villanueva Medina, Garba M. Khalid, Hemanth Kumar Boyina, Milen Georgiev, Claudiu T. Supuran, Eduardo Sobarzo-Sanchez, Tai-Ping Fan, Valeria Pittala, Antoni Sureda, Nady Braidy, Gian Luigi Russo, Rosa Anna Vacca, Maciej Banach, Gerard Lizard, Amira Zarrouk, Sonia Hammami, Ilkay Erdogan Orhan, Bharat B. Aggarwal, George Perry, Mark J. S. Miller, Michael Heinrich, Anupam Bishayee, Anake Kijjoa, Nicolas Arkells, David Bredt, Michael Wink, Bernd L. Fiebich, Gangarapu Kiran, Andy Wai Kan Yeung, Girish Kumar Gupta, Antonello Santini, Massimo Lucarini, Alessandra Durazzo, Amr El-Demerdash, Albena T. Dinkova-Kostova, Alejandro Cifuentes, Eliana B. Souto, Muhammad Asim Masoom Zubair, Pravin Badhe, Javier Echeverria, Jaroslaw Olav Horbanczuk, Olaf K. Horbanczuk, Helen Sheridan, Sadeeq Muhammad Sheshe, Anna Maria Witkowska, Ibrahim M. Abu-Reidah, Muhammad Riaz, Hammad Ullah, Akolade R. Oladipupo, Victor Lopez, Neeraj Kumar Sethiya, Bhupal Govinda Shrestha, Palaniyandi Ravanan, Subash Chandra Gupta, Qushmua E. Alzahrani, Preethidan Dama Sreedhar, Jianbo Xiao, Mohammad Amin Moosavi, Parasuraman Aiya Subramani, Amit Kumar Singh, Ananda Kumar Chettupalli, Jayanta Kumar Patra, Gopal Singh, Tomasz M. Karpinski, Fuad Al-Rimawi, Rambod Abiri, Atallah F. Ahmed, Davide Barreca, Sharad Vats, Said Amrani, Carmela Fimognari, Andrei Mocan, Lucian Hritcu, Prabhakar Semwal, Md Shiblur Rahaman, Mila Emerald, Akinleye Stephen Akinrinde, Abhilasha Singh, Ashima Joshi, Tanuj Joshi, Shafaat Yar Khan, Gareeballah Osman Adam Balla, Aiping Lu, Sandeep Ramchandra Pai, Imen Ghzaiel, Niyazi Acar, Nour Eddine Es-Safi, Gokhan Zengin, Azazahemad A. Kureshi, Arvind Kumar Sharma, Bikash Baral, Neeraj Rani, Philippe Jeandet, Monica Gulati, Bhupinder Kapoor, Yugal Kishore Mohanta, Zahra Emam-Djomeh, Raphael Onuku, Jennifer R. Depew, Omar M. Atrooz, Bey Hing Goh, Jose Carlos Andrade, Bikramjit Konwar, V. J. Shine, Joao Miguel Lousa Dias Ferreira, Jamil Ahmad, Vivek K. Chaturvedi, Krystyna Skalicka-Wozniak, Rohit Sharma, Rupesh K. Gautam, Sebastian Granica, Salvatore Parisi, Rishabh Kumar, Atanas G. Atanasov, Bairong Shen
Summary: The development of digital technologies and open innovation approaches has enabled the creation of virtual organizations and enterprises. The International Natural Product Sciences Taskforce (INPST) is an open innovation platform that brings together individuals and organizations interested in natural product scientific research. This study presents an overview of INPST activities and showcases the use of Twitter as a powerful networking tool, demonstrated through the 2021 INPST Twitter Networking Event.
Article
Multidisciplinary Sciences
Kang-Li Hsieh, German Plascencia-Villa, Ko-Hon Lin, George Perry, Xiaoqian Jiang, Yejin Kim
Summary: To overcome the challenges in Alzheimer's disease drug development, researchers developed a multi-task deep learning pipeline that learns biological interactions and AD risk genes to identify repurposable drug candidates based on multi-level evidence. Mechanistic validation in neuronal cells confirmed several biologically efficacious drug combinations for reducing oxidative stress and maintaining neuronal viability and morphology. This pipeline highlights the importance of harmonizing heterogeneous and complementary data/knowledge for drug development of complex diseases.
Review
Clinical Neurology
Richard Lathe, Nikki M. Schultek, Brian J. Balin, Garth D. Ehrlich, Lavinia Alberi Auber, George Perry, Edward B. Breitschwerdt, David B. Corry, Richard L. Doty, Robert A. Rissman, Peter L. Nara, Ruth Itzhaki, William A. Eimer, Rudolph E. Tanzi
Summary: Microbial infections can cause dementia, and their role in Alzheimer's disease (AD) pathology has long been debated. The lack of standardized detection methods has resulted in inconsistent identification of microbes in AD brains. The Alzheimer's Pathobiome Initiative aims to compare microbes in various samples to establish a consensus methodology for detection. If successful, this could lead to tailored antimicrobial treatments for patients with mild cognitive impairment or AD, potentially improving clinical outcomes.
ALZHEIMERS & DEMENTIA
(2023)
Review
Ophthalmology
Moein Ebrahimi, Paul Thompson, Andreas K. Lauer, Sobha Sivaprasad, George Perry
Summary: Diabetic retinopathy is a major cause of vision loss and blindness, and while the changes in the retina have been extensively studied, the impact of diabetes on the rest of the visual system has been less explored. Simultaneous investigation of the retina and the brain may shed light on the neurodegenerative mechanisms in diabetics, as well as the shared mechanisms between diabetic retinopathy and other neurodegenerative disorders like Alzheimer's and Parkinson's disease.
EUROPEAN JOURNAL OF OPHTHALMOLOGY
(2023)
Editorial Material
Neurosciences
Craig S. Atwood, George Perry
Summary: The approval of aducanumab and lecanemab by the FDA has sparked debate over their safety and efficacy. This article discusses the important physiological functions of amyloid-beta as a barrier protein, including its sealant and anti-pathogenic activities that help maintain vascular integrity and prevent encephalitis and meningitis. Approving drugs that undermine these functions may increase the risk of hemorrhage, edema, and other negative outcomes, which should be clearly communicated to patients.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Multidisciplinary Sciences
Parnian Shobeiri, Sanam Alilou, Mehran Jaberinezhad, Farshad Zare, Nastaran Karimi, Saba Maleki, Antonio L. Teixeira, George Perry, Nima Rezaei
Summary: This systematic review evaluated the accuracy of long non-coding RNAs (lncRNAs) in identifying Alzheimer's disease (AD) through meta-analysis. The results showed that lncRNAs had high accuracy in identifying AD and could be considered a promising diagnostic biomarker for the disease.
Article
Neurosciences
Wenzhang Wang, Fanpeng Zhao, Yubing Lu, Sandra L. Siedlak, Hisashi Fujioka, Hao Feng, George Perry, Xiongwei Zhu
Summary: Loss of synapses is the most significant pathological feature of Alzheimer's disease (AD) that leads to cognitive deficits. This study examined synaptic deficits in AD patients and found that mitochondrial dysfunction in both pre- and post-synaptic compartments contribute to synaptic deficits in AD. These findings provide further evidence of the importance of mitochondrial dysfunction in AD pathology.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Information Science & Library Science
Mahsa Keshavarz-Fathi, Niloufar Yazdanpanah, Sajad Kolahchi, Heliya Ziaei, Gary L. Darmstadt, Tommaso Dorigo, Filip Dochy, Lisa Levin, Visith Thongboonkerd, Shuji Ogino, Wei-Hsin Chen, Matjaz Perc, Mark S. Tremblay, Bolajoko O. Olusanya, Idupulapati M. Rao, Nikos Hatziargyriou, Maziar Moradi-Lakeh, Federico Bella, Laszlo Rosivall, Amir H. Gandomi, Armin Sorooshian, Manoj Gupta, Ciprian Gal, Andres M. Lozano, Connie Weaver, Michael Tanzer, Alessandro Poggi, Sadaf G. Sepanlou, Ralf Weiskirchen, Anet Rezek Jambrak, Pedro J. Torres, Esra Capanoglu, Francisco J. Barba, Chua Kian Jon Ernest, Mariano Sigman, Stefano Pluchino, Gevork B. Gharehpetian, Seyed-Mohammad Fereshtehnejad, Muh-Hwa Yang, Sabu Thomas, Wenju Cai, Elisabetta Comini, Neil J. Scolding, Paul S. Myles, Juan J. Nieto, George Perry, Constantine Sedikides, Nima Rezaeia
Summary: Scientometrics and bibliometrics are subfields of library and information science that study the quantity and quality of research outputs. The h-index is the most well-known scientometric index, but it relies on the count of highly cited publications. To address this limitation, we developed a new index called the Universal Research Index (UR-Index) that considers the impact of every single publication. We incorporated additional variables such as publication type, leading role, co-author count, and source metrics into the UR-Index. However, we recognize that unconscious biases in these variables may disadvantage research from specific groups, and encourage efforts to improve equitable scholarly impact in science and academia.
JOURNAL OF ACADEMIC LIBRARIANSHIP
(2023)
Article
Clinical Neurology
Harald Hampel, Yan Hu, John Hardy, Kaj Blennow, Christopher Chen, George Perry, Seung Hyun Kim, Victor L. Villemagne, Paul Aisen, Michele Vendruscolo, Takeshi Iwatsubo, Colin L. Masters, Min Cho, Lars Lannfelt, Jeffrey L. Cummings, Andrea Vergallo
Summary: This summary reviews the evidence supporting the role of the amyloid-b (Ab) pathway in Alzheimer's disease (AD) and emphasizes the importance of targeting this pathway in early stages of the disease. Understanding and targeting the A beta pathway can lead to better therapeutic outcomes and management of AD.
NEURODEGENERATIVE DISEASE MANAGEMENT
(2023)
Book Review
Neurosciences
George Perry
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Review
Biochemistry & Molecular Biology
German Plascencia-Villa, George Perry
Summary: Alzheimer's disease is a progressive brain disorder characterized by memory and thinking impairment, with various pathological features such as abnormal protein aggregates, synaptic dysfunction, and oxidative stress. Oxidative stress, often overlooked or considered a consequence of dementia, plays a crucial role in AD progression and neuronal death. Recognizing oxidative stress as a key factor in AD has led to the development of alternative therapeutic interventions and preventive strategies for this devastating neurodegenerative disease.
Article
Medicine, General & Internal
Poul F. Hoilund-Carlsen, Mona-Elisabeth Revheim, Tommaso Costa, Kasper P. Kepp, Rudolph J. Castellani, George Perry, Abass Alavi, Jorge R. Barrio
Summary: In June 2021, the FDA accelerated approved aducanumab and in January 2023 also lecanemab, based on perceived drug-induced removal of cerebral amyloid-beta as assessed by amyloid-PET and, in the case of lecanemab, limited clinical efficacy assumption. Approval for donanemab is pending further data. However, published trial data indicate minimal and uncertain clinical benefits, similar to conventional medication. Additionally, amyloid-PET signal decrease may reflect increased cell damage instead of amyloid removal, as supported by increased amyloid-related imaging abnormalities and brain volume loss in treated patients compared to placebo. We also question the current AD diagnostic criteria based on amyloid-PET imaging biomarkers and recommend future anti-AD therapy trials to incorporate (1) diagnosis based on cognitive decline and decreased cerebral metabolism assessed by FDA-approved FDG-PET, (2) therapy efficacy determined by cognitive ability, cerebral metabolism by FDG-PET, and brain volumes by MRI, and (3) neuropathologic examination of all deaths occurring in these trials.