Article
Clinical Neurology
Zhi Ruan, Dhruba Pathak, Srinidhi Venkatesan Kalavai, Asuka Yoshii-Kitahara, Satoshi Muraoka, Nemil Bhatt, Kayo Takamatsu-Yukawa, Jianqiao Hu, Yuzhi Wang, Samuel Hersh, Maria Ericsson, Santhi Gorantla, Howard E. Gendelman, Rakez Kayed, Seiko Ikezu, Jennifer Luebke, Tsuneya Ikezu
Summary: This study comprehensively characterized the physicochemical structure and pathogenic function of extracellular vesicles derived from human brains in Alzheimer's disease, prodromal Alzheimer's disease, and non-demented control cases. It was found that extracellular vesicles from Alzheimer's disease cases had higher levels of tau oligomers and exhibited more efficient propagation and misfolding of tau, suggesting a novel mechanism for tau spread in the hippocampus.
Article
Clinical Neurology
Juan Carlos Polanco, Gabriel Rhys Hand, Adam Briner, Chuanzhou Li, Jurgen Gotz
Summary: The study revealed that tau seeds in tauopathies spread trans-synaptically via exosomes, escaping endosomes through lysosomal degradation to induce tau aggregation in the cytosol. The enzymatic activities of lysosomes permeabilize exosomal and endosomal membranes, facilitating access of exosomal tau seeds to cytosolic tau for aggregation. This highlights the crucial role of endosomal membrane integrity in cellular invasion by misfolded proteins resistant to lysosomal degradation.
ACTA NEUROPATHOLOGICA
(2021)
Article
Immunology
Jiahui Zhu, Xingjun Jiang, Yanmin Chang, Yanqing Wu, Shangqi Sun, Cailin Wang, Siyi Zheng, Min Wang, Yi Yao, Gang Li, Rong Ma
Summary: The study found that clemastine fumarate shows potential in treating Alzheimer's disease. It reduces Tau protein deposition, protects neurons and synapses, reduces neuroinflammation, and improves cognitive function.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Arunkumar Subramanian, T. Tamilanban, Abdulrhman Alsayari, Gobinath Ramachawolran, Ling Shing Wong, Mahendran Sekar, Siew Hua Gan, Vetriselvan Subramaniyan, Suresh V. V. Chinni, Nur Najihah Izzati Mat Rani, Nagaraja Suryadevara, Shadma Wahab
Summary: The primary and significant weakening event in elderly individuals is age-dependent cognitive decline and dementia, with Alzheimer's disease being the chief cause. Understanding the molecular mechanisms underlying Alzheimer's disease and other cognitive deficits is crucial. The regulatory relationship between the mammalian target of rapamycin (mTOR) signaling pathway and Alzheimer's disease, as well as the role of autophagy, is pivotal. Exploring the link between mTOR and autophagy further holds potential for Alzheimer's disease therapy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Yuxing Xia, Brach M. M. Bell, Justin D. D. Kim, Benoit I. I. Giasson
Summary: Tauopathies are neurodegenerative diseases characterized by the formation of tau brain aggregates. Imbalance of 3R and 4R tau isoforms is a contributing factor in the development of these diseases. The S356T tau mutation shows unique prion-like seeded aggregation, forming extensive Thioflavin positive aggregates. This finding will contribute to the understanding of diverse presentations of different tauopathies.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Pharmacology & Pharmacy
Majedul Islam, Fengyun Shen, Deepika Regmi, Deguo Du
Summary: Tauopathies are neurodegenerative diseases characterized by abnormal tau deposition in the brain. Currently, there are no approved disease-modifying therapies for tauopathies. Drug repurposing offers a potential alternative approach to discover effective drugs for treating these diseases.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Cell Biology
Zhi-Sheng Ji, Jian-Ping Li, Chao-Hua Fu, Jian-Xian Luo, Hua Yang, Guo-Wei Zhang, Wutian Wu, Hong-Sheng Lin
Summary: The study showed that the protein CRMP3 plays a key role in the repair process of spinal cord injury, interacting with spastin to promote neurite growth and branching. It was also demonstrated that overexpression of CRMP3 enhances the ability of spastin to promote neurite growth. Therefore, spastin and CRMP3 participate in spinal cord injury repair by regulating neurite growth and branching.
NEURAL REGENERATION RESEARCH
(2021)
Article
Clinical Neurology
Batbayar Tumurbaatar, Anna Fracassi, Pietro Scaduto, Jutatip Guptarak, Randall Woltjer, Daniel Jupiter, Giulio Taglialatela
Summary: This study investigates the association of autophagy with cognitive integrity in individuals with Alzheimer's disease neuropathology but without dementia. The results suggest that preserved autophagy may protect against cognitive decline in these individuals.
ALZHEIMERS & DEMENTIA
(2023)
Review
Oncology
Rayane Hedna, Herve Kovacic, Alessandra Pagano, Vincent Peyrot, Maxime Robin, Francois Devred, Gilles Breuzard
Summary: Tau protein plays a crucial role in neurodegenerative diseases, but recent studies have shown its involvement in cancer progression and treatment resistance. This review focuses on the role of Tau in glioblastoma and sheds light on its mechanistic involvement in oncogenic processes. It also discusses the potential of Tau as a therapeutic target for glioblastoma treatment.
Review
Neurosciences
Zhongya Gu, Huan Cao, Chengchao Zuo, Yaqi Huang, Jinfeng Miao, Yu Song, Yuyan Yang, Liudi Zhu, Furong Wang
Summary: This review focuses on the pathological mechanisms of Alzheimer's disease and highlights the research progress and therapeutic approaches related to TFEB, a transcription factor involved in autophagy regulation. It provides important insights into the treatment strategies and clinical management of AD.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Pharmacology & Pharmacy
Juan Li, Bin Zou, Xiao-Yu Cheng, Xin-He Yang, Jia Li, Chun-Hui Zhao, Rui-Xia Ma, Ji-Xiang Tian, Yao Yao
Summary: This study found that total saikosaponins (TS) could ameliorate cognitive dysfunction in Alzheimer's disease (AD) by activating nuclear factor 2 (Nrf2) and downregulating the expression of beta-secretase 1 (BACE1), reducing the generation of amyloid-beta (A beta) and senile plaque deposition. TS also enhanced autophagy, inhibited the activation of nuclear factor-kappa B (NF-kappa B), and improved synaptic loss and oxidative stress.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Xing Jun Jiang, Yan Qing Wu, Rong Ma, Yan Min Chang, Lu Lu Li, Jia Hui Zhu, Gong Ping Liu, Gang Li
Summary: This study found that overexpression of PINK1 can promote the degradation of accumulated tau proteins in patients with AD, improving cognitive abilities and rescuing damaged neurons and synapses. Furthermore, PINK1 also improves mitochondrial dysfunction caused by tau proteins. This suggests that PINK1 may be a potential target for AD treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Wei Zhang, Chengchao Xu, Jichao Sun, Han-Ming Shen, Jigang Wang, Chuanbin Yang
Summary: Alzheimer's disease is a common neurodegenerative disorder characterized by memory loss and cognitive dysfunction. Impaired autophagy-lysosomal pathway is linked to AD pathogenesis, and enhancing autophagy to remove protein aggregates is proposed as a promising therapeutic strategy.
ACTA PHARMACEUTICA SINICA B
(2022)
Review
Biochemistry & Molecular Biology
Tadanori Hamano, Soichi Enomoto, Norimichi Shirafuji, Masamichi Ikawa, Osamu Yamamura, Shu-Hui Yen, Yasunari Nakamoto
Summary: Neurofibrillary tangles and senile plaques are pathological hallmarks of Alzheimer's disease, with autophagy disturbances being implicated in tau protein accumulation. Therapeutic strategies focusing on autophagic modulation may hold promise in AD treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Gaoping Lin, Feiyan Zhu, Nicholas M. Kanaan, Rei Asano, Norimichi Shirafuji, Hirohito Sasaki, Tomohisa Yamaguchi, Soichi Enomoto, Yoshinori Endo, Asako Ueno, Masamichi Ikawa, Kouji Hayashi, Osamu Yamamura, Shu-Hui Yen, Yasunari Nakamoto, Tadanori Hamano
Summary: The neuropathological features of Alzheimer's disease are senile plaques and neurofibrillary tangles, which are composed of amyloid beta protein and phosphorylated tau protein respectively. Metal regulation, especially with compounds like clioquinol, may be a potential direction for AD treatment. Clioquinol has been shown to decrease metal accumulation, tau phosphorylation, and activate pathways involved in tau protein degradation, potentially offering new insights into AD therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Vebjorn Martinsen, Petri Kursula
Summary: MBP is an abundant protein in CNS myelin and is studied in relation to the pathogenesis of MS. While its direct role as a primary antigen in human MS is unclear, MBP and its functions in myelin formation and maintenance are linked to the disease. This molecule demonstrates the complex relationship between normal nervous system development and neurodegenerative disease.
Article
Biochemistry & Molecular Biology
Abris Adam Bendes, Petri Kursula, Inari Kursula
Summary: Apicomplexan parasites rely on the glideosome for motility and host cell invasion; actin filament capping proteins (CPs) play a crucial role in regulating actin dynamics; this study presents the crystal structure of CP from the malaria parasite and reveals differences compared to canonical heterodimers.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Correction
Cell Biology
Arne Raasakka, Petri Kursula
Article
Biochemistry & Molecular Biology
Laura Kind, Arne Raasakka, Janne Molnes, Ingvild Aukrust, Lise Bjorkhaug, Pal Rasmus Njolstad, Petri Kursula, Thomas Arnesen
Summary: In this study, the structure and function of HNF-1A were analyzed, and several pathogenic variants related to MODY3 were identified. These findings are important for precise diagnosis and treatment of diabetes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Correction
Biochemistry & Molecular Biology
Yuta Ishizuka, Tadiwos F. Mergiya, Rodolfo Baldinotti, Ju Xu, Erik I. Hallin, Sigurbjorn Markusson, Petri Kursula, Clive R. Bramham
NEUROCHEMICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Yuta Ishizuka, Tadiwos F. Mergiya, Rodolfo Baldinotti, Ju Xu, Erik Hallin, Sigurbjorn Markusson, Petri Kursula, Clive R. Bramham
Summary: Arc protein plays important roles in synaptic plasticity, memory, and cognitive flexibility. This study developed anti-Arc nanobodies as new tools to investigate Arc dynamics and function, and found that ArcNbs have versatile applications.
NEUROCHEMICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Aleksi Sutinen, Giang Thi Tuyet Nguyen, Arne Raasakka, Gopinath Muruganandam, Remy Loris, Emil Ylikallio, Henna Tyynismaa, Luca Bartesaghi, Salla Ruskamo, Petri Kursula
Summary: This study investigates the biochemical and structural properties of GDAP1 gene mutations causing Charcot-Marie-Tooth disease. The findings reveal that these mutations lead to alterations in GDAP1 structure and decreased thermal stability, resulting in insufficient neuronal function.
Correction
Biochemistry & Molecular Biology
Giang Thi Tuyet Nguyen, Aleksi Sutinen, Arne Raasakka, Gopinath Muruganandam, Remy Loris, Petri Kursula
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Salla Ruskamo, Arne Raasakka, Jan Skov Pedersen, Anne Martel, Karel Skubnik, Tamim Darwish, Lionel Porcar, Petri Kursula
Summary: This study characterized the three-dimensional structure and functional differences of the most abundant protein in myelin, PLP, and its isoform DM20, and revealed the mechanisms of their interactions with lipids. Reconstituted PLP and DM20 spontaneously induced the formation of multi-layered membrane structures similar to myelin in the lipid bilayers. These findings contribute to a better understanding of the organization and function of proteins in compact myelin in the central nervous system.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Sigurbjorn Markusson, Erik Hallin, Helene J. Bustad, Arne Raasakka, Ju Xu, Gopinath Muruganandam, Remy Loris, Aurora Martinez, Clive R. Bramham, Petri Kursula
Summary: Activity-regulated cytoskeleton-associated protein (Arc) plays a vital role in synaptic plasticity and memory formation. This study used high-affinity anti-Arc nanobodies to investigate the structure and function of Arc. The results suggest that the N-terminal domain of Arc is involved in membrane binding, while the C-terminal domain binds to postsynaptic protein ligands. Furthermore, the NTD and CTD are important for Arc oligomerisation and assembly of capsids.
Article
Genetics & Heredity
Mirella Vinci, Petri Kursula, Donatella Greco, Maurizio Elia, Luigi Vetri, Carmelo Schepis, Valeria Chiavetta, Serena Donadio, Michele Roccella, Marco Carotenuto, Valentino Romano, Francesco Cali
Summary: This study reports a case of CFC-like phenotype in a patient with compound heterozygote missense mutations in the AHNAK2 gene. The mutations were found to be unrelated to known genes associated with CFC syndrome, and their impact on protein function was predicted to be not severe. The mutations were located in flexible regions possibly involved in molecular interactions.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Sigurbjorn Markusson, Jens G. Hjorleifsson, Petri Kursula, Bjarni Asgeirsson
Summary: This study reveals the presence of two chloride binding sites in the structure of marine bacterial alkaline phosphatase (VAP), one in the active site and another at a peripheral site. Binding of chloride ions to the peripheral site decreases structural dynamics, leading to thermal stabilization of the VAP active conformation. The binding of chloride ion in the active site does not displace the bound inorganic phosphate product, but it may promote product release by facilitating rotational stabilization of the substrate-binding Arg129.
Article
Multidisciplinary Sciences
Aleksi Sutinen, Dirk Paffenholz, Giang Thi Tuyet Nguyen, Salla Ruskamo, Andrew E. Torda, Petri Kursula
Summary: Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral polyneuropathy in humans, and its subtypes are linked to mutations in dozens of different genes, including the gene coding for ganglioside-induced differentiation-associated protein 1 (GDAP1). The etiology of GDAP1-linked CMT is poorly understood at the protein level, despite implications for mitochondrial fission and fusion, cytoskeletal interactions, and response to reactive oxygen species. Structural and biophysical analyses on several CMT-linked GDAP1 protein variants have been carried out, and new crystal structures of these variants have been described.
Article
Biochemistry & Molecular Biology
Dorothee Houry, Arne Raasakka, Eugenio Ferrario, Marc Niere, Ersilia Bifulco, Petri Kursula, Mathias Ziegler
Summary: In this study, the mechanism of increased substrate affinity of phosphorylated NAMPT is revealed, which includes the coordination of Mg2+ by phospho-His247 to stabilize PRPP in a position favorable for catalysis. Additionally, a stretch of 10 amino acids found only in NAMPTs from deuterostomes is shown to enhance conformational plasticity and stabilize the chemically unstable phosphorylation of His247. Overall, this study provides a structural basis for the important function of NAMPT in recycling Nicotinamide into NAD biosynthesis with high affinity.
JOURNAL OF STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Oda C. Krokengen, Arne Raasakka, Petri Kursula
Summary: Numerous human proteins, known as intrinsically disordered proteins (IDPs), lack high-resolution structural information due to their physicochemical properties. However, IDPs can adopt local ordered structures upon interaction with other proteins or lipid membranes. Using AlphaFold2 predictions and experimental data, we have found that the predicted models of two myelin-specific IDPs closely match their membrane-binding sites. These artificial intelligence-based models provide insight into the ligand-bound state of IDPs and are crucial for understanding the role of IDPs in diseases.
BIOCHEMISTRY AND BIOPHYSICS REPORTS
(2023)