Review
Cell Biology
Daniel Ruiz-Gabarre, Almudena Carnero-Espejo, Jesus Avila, Vega Garcia-Escudero
Summary: Tau protein, encoded by the MAPT gene, has multiple physiological functions and is associated with various pathologies. The splicing of MAPT transcripts is complex, generating multiple isoforms that are spatially and developmentally regulated. These Tau isoforms play important roles in both physiology and pathology.
Article
Biochemistry & Molecular Biology
Emma S. Davies, Russell M. Morphew, David Cutress, A. Jennifer Morton, Sebastian McBride
Summary: Alzheimer's disease is a chronic neurodegenerative disease, and the exact mechanism and pathological characteristics are still unclear. Recent studies have suggested that rodent models are not adequate for studying the disease, leading to increased attention on alternative animal models, such as sheep. This study found that sheep naturally exhibit beta-amyloid and tau pathologies similar to early stages of Alzheimer's disease, which highlights the importance of using sheep as a feasible large animal model for studying the disease.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Neurosciences
Suelen Santos Alves, Rui Milton Patricio da Silva Junior, Polianna Delfino-Pereira, Marilia Gabriella Alves Goulart Pereira, Israel Vasconcelos, Hanna Schwaemmle, Rodrigo Focosi Mazzei, Maiko Luiz Carlos, Enilza Maria Espreafico, Antonio Claudio Tedesco, Adriano Sebollela, Sebastiao Sousa Almeida, Jose Antonio Cortes de Oliveira, Norberto Garcia-Cairasco
Summary: This study explores the behavioral and molecular alterations related to Alzheimer's disease in a genetic model of epilepsy. The findings indicate a partial AD-like phenotype, characterized by altered insulin signaling, in the epilepsy model. The study contributes to the understanding of the connection between epilepsy and AD, highlighting potential therapeutic targets.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Neurosciences
Zuha Waheed, Jawaria Choudhary, Faria Hasan Jatala, Aneeqa Noor, Inga Zerr, Saima Zafar
Summary: Tau is a microtubule-associated binding protein in the nervous system that stabilizes microtubules in nerve cells. It accumulates as aggregates and tangles, leading to various pathologies. Different splice variants of tau are expressed in the brain and contribute to neurodegenerative diseases. The isoforms have different roles and undergo post-translational modifications at different rates, affecting their physiological and pathological attributes. This article aims to review the roles of tau isoforms and their underlying mechanisms in neurological deficits.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Chihiro Sato, Nipun Mallipeddi, Nupur Ghoshal, Brenton A. Wright, Gregory S. Day, Albert A. Davis, Albert H. Kim, Gregory J. Zipfel, Randall J. Bateman, Audrey Gabelle, Nicolas R. Barthelemy
Summary: High pT217/T217 and low Aβ42/40 were found in CSF of AD patients, while low pT217/T217 and normal Aβ42/40 were observed in 3R+4R tauopathies patients and cognitively normal individuals. The CSF pT217/T217 x CSF Aβ42/40 composite biomarker is sensitive in distinguishing MAPT R406W carriers from other groups.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Neurosciences
Mette Habekost, Per Qvist, Mark Denham, Ida E. Holm, Arne Lund Jorgensen
Summary: The study reveals that induced neurons from reprogramming of other cell types need extended in vitro culture to express tau isoforms characteristic of adult neurons; Research on porcine and murine cerebral cortices shows age-dependent and species-specific isoform composition of MAPT; Induced neurons directly converted from fibroblasts exhibit developmental patterns of isoform composition related to the pathogenesis of Alzheimer's disease.
MOLECULAR NEUROBIOLOGY
(2021)
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
Neurosciences
Suelen Santos Alves, Rui Milton Patricio da Silva-Junior, Gabriel Servilha-Menezes, Jan Homolak, Melita Salkovic-Petrisic, Norberto Garcia-Cairasco
Summary: Alzheimer's disease is a severe public health problem and current medical approaches are limited to symptomatic interventions, with a high failure rate in clinical trials. While most studies have focused on the amyloid cascade hypothesis, it is clear that AD is a multifactorial disorder.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Multidisciplinary Sciences
Yin Xu, Nicholas E. Propson, Shuqi Du, Wen Xiong, Hui Zheng
Summary: Studies indicate that microglial-specific autophagy, represented by Atg7, plays a crucial role in regulating lipid metabolism and neuroinflammation. Deletion of Atg7 in microglia leads to a proinflammatory status and exacerbates intraneuronal tau pathology.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Toshitaka Ochiai, Toshiharu Sano, Takeru Nagayama, Naoto Kubota, Takashi Kadowaki, Tomoko Wakabayashi, Takeshi Iwatsubo
Summary: The study found that IRS-2 plays a dominant role in brain IIS and supports the hypothesis that reduced IIS exerts anti-amyloid effects in the brain.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Medicine, General & Internal
Anna Baran, Julia Nowowiejska, Justyna Magdalena Hermanowicz, Beata Sieklucka, Julita Anna Krahel, Paulina Kiluk, Dariusz Pawlak, Iwona Flisiak
Summary: There is an association between psoriasis and neurodegenerative diseases. Treatment with methotrexate has neuroprotective properties.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Neurosciences
Caleigh A. Findley, Samuel A. McFadden, MaKayla F. Cox, Lindsey N. Sime, Mackenzie R. Peck, Kathleen Quinn, Andrzej Bartke, Kevin N. Hascup, Erin R. Hascup
Summary: This study investigates the relationship between Alzheimer's disease and metabolic dysfunction, and finds that modulation of glutamatergic activity can improve glucose metabolism and spatial cognition, providing a new therapeutic approach for cognitive decline.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Neurosciences
Andres Norambuena, Xuehan Sun, Horst Wallrabe, Ruofan Cao, Naidi Sun, Evelyn Pardo, Nutan Shivange, Dora Bigler Wang, Lisa A. Post, Heather A. Ferris, Song Hu, Ammasi Periasamy, George S. Bloom
Summary: This study reveals a novel mechanism of mitochondrial DNA synthesis in Alzheimer's disease, where nutrient-stimulated lysosomal mTORC1 activity regulates mtDNA replication in neurons. The study also shows a link between tau and superoxide dismutase 1 (SOD1) to mitochondrial dysfunction and Alzheimer's disease.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Clinical Neurology
David Wallon, Susana Boluda, Anne Rovelet-Lecrux, Manon Thierry, Julien Lagarde, Laetitia Miguel, Magalie Lecourtois, Antoine Bonnevalle, Marie Sarazin, Michel Bottlaender, Mathieu Mula, Serge Marty, Natsuko Nakamura, Catherine Schramm, Francois Sellal, Therese Jonveaux, Camille Heitz, Isabelle Le Ber, Stephane Epelbaum, Eloi Magnin, Aline Zarea, Stephane Rousseau, Olivier Quenez, Didier Hannequin, Florence Clavaguera, Dominique Campion, Charles Duyckaerts, Gael Nicolas
Summary: Microduplications of the 17q21.31 chromosomal region containing the MAPT gene have been found in patients with a progressive disorder characterized by memory impairment, behavioral changes, and atypical extrapyramidal syndrome. Neuropathological examination shows Tau protein deposits with a spectrum of 3R- and 4R-tau aggregates.
ACTA NEUROPATHOLOGICA
(2021)
Article
Behavioral Sciences
Suelen Santos Alves, Gabriel Servilha-Menezes, Leticia Rossi, Rui Milton Patricio da Silva Junior, Norberto Garcia-Cairasco
Summary: Since glucose reuptake by neurons is mostly independent of insulin, it has been a question whether insulin has any roles in the brain. The identification of insulin receptors in the central nervous system has fueled investigations of insulin functions in the brain. It is known that insulin can influence glucose reuptake by neurons, especially during high energy-demand activities. The high density of insulin receptors in the hippocampus suggests important roles of insulin related to memory. In this context, disturbed insulin signaling in experimental animal models of Alzheimer's disease (AD) is reviewed.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Article
Evolutionary Biology
Guilherme Braga de Freitas, Rafaella Araujo Goncalves, Matthias Gralle
BMC EVOLUTIONARY BIOLOGY
(2016)
Article
Multidisciplinary Sciences
Xiaobo Mao, Michael Tianhao Ou, Senthilkumar S. Karuppagounder, Tae-In Kam, Xiling Yin, Yulan Xiong, Preston Ge, George Essien Umanah, Saurav Brahmachari, Joo-Ho Shin, Ho Chul Kang, Jianmin Zhang, Jinchong Xu, Rong Chen, Hyejin Park, Shaida A. Andrabi, Sung Ung Kang, Rafaella Araujo Goncalves, Yu Liang, Shu Zhang, Chen Qi, Sharon Lam, James A. Keiler, Joel Tyson, Donghoon Kim, Nikhil Panicker, Seung Pil Yun, Creg J. Workman, Dario A. A. Vignali, Valina L. Dawson, Han Seok Ko, Ted M. Dawso
Article
Biochemistry & Molecular Biology
Nadeeja Wijesekara, Rafaella Araujo Goncalves, Rosemary Ahrens, Fernanda G. De Felice, Paul E. Fraser
Review
Neurosciences
Nadeeja Wijesekara, Rafaella Araujo Goncalves, Fernanda G. De Felice, Paul E. Fraser
Article
Biochemistry & Molecular Biology
Mychael V. Lourenco, Rudimar L. Frozza, Guilherme B. de Freitas, Hong Zhang, Grasielle C. Kincheski, Felipe C. Ribeiro, Rafaella A. Goncalves, Julia R. Clarke, Danielle Beckman, Agnieszka Staniszewski, Hanna Berman, Lorena A. Guerra, Leticia Forny-Germano, Shelby Meier, Donna M. Wilcock, Jorge M. de Souza, Soniza Alves-Leon, Vania F. Prado, Marco A. M. Prado, Jose F. Abisambra, Fernanda Tovar-Moll, Paulo Mattos, Ottavio Arancio, Sergio T. Ferreira, Fernanda G. De Felice
Article
Neurosciences
Natalia de M. Lyra e Silva, Rafaella Araujo Goncalves, Susan E. Boehnke, Leticia Forny-Germano, Douglas P. Munoz, Fernanda G. De Felice
EXPERIMENTAL NEUROLOGY
(2019)
Review
Neurosciences
Rafaella Araujo Goncalves, Nadeeja Wijesekara, Paul E. Fraser, Fernanda G. De Felice
FRONTIERS IN CELLULAR NEUROSCIENCE
(2019)
Review
Biochemistry & Molecular Biology
Melina Paula Bordone, Mootaz M. Sahnan, Haley E. Titus, Main Amini, Jens V. Andersen, Barnali Chakraborti, Artem V. Diuba, Tatsiana G. Dubouskaya, Eric Ehrke, Andiara Espindola de Freitas, Guilherme Braga de Freitas, Rafaella A. Goncalves, Deepali Gupta, Richa Gupta, Sharon R. Ha, Isabel A. Hemming, Minal Jaggar, Emil Jakobsen, Punita Kumari, Navya Lakkappa, Ashley P. L. Marsh, Jessica Mitloehner, Yuki Ogawa, Paidi Ramesh Kumar, Felipe C. Ribeiro, Ahmad Salamian, Suraiya Saleem, Sorabh Sharma, Joana M. Silva, Shripriya Singh, Kunjbihari Sulakhiya, Tesfaye Wolde Tefera, Behnam Vafadari, Anuradha Yadav, Reiji Yamazaki, Constanze I. Seidenbecher
JOURNAL OF NEUROCHEMISTRY
(2019)
Article
Oncology
Nadeeja Wijesekara, Rafaella Araujo Goncalves, Rosemary Ahrens, Kathy Ha, Fernanda G. De Felice, Paul E. Fraser
Summary: The combined effects of human tau and human IAPP in transgenic mice led to increased hyperglycaemia, insulin resistance, and glucose intolerance, reduced beta cell area and insulin content, increased amyloid deposition, and impaired insulin processing. This suggests a potential mechanism connecting Alzheimer's disease and type 2 diabetes through a coordinated impairment of beta cell function and glucose homeostasis by tau and IAPP amyloid.
JOURNAL OF PATHOLOGY
(2021)
Article
Psychiatry
Natalia M. Lyra e Silva, Rafaella A. Goncalves, Tharick A. Pascoal, Ricardo A. S. Lima-Filho, Elisa de Paula Franca Resende, Erica L. M. Vieira, Antonio L. Teixeira, Leonardo C. de Souza, Julyanna A. Peny, Juliana T. S. Fortuna, Isadora C. Furigo, Debora Hashiguchi, Vivian S. Miya-Coreixas, Julia R. Clarke, Jose F. Abisambra, Beatriz M. Longo, Jose Donato, Paul E. Fraser, Pedro Rosa-Neto, Paulo Caramelli, Sergio T. Ferreira, Fernanda G. De Felice
Summary: Alzheimer's disease is associated with cognitive impairment and metabolic alterations, with mounting evidence suggesting that abnormal signaling in a brain-periphery metabolic axis plays a crucial role in its pathophysiology. The IL-6 pathway may serve as a key link between memory dysfunction and metabolic changes in AD. Targeting pro-inflammatory IL-6 signaling could be a strategy to alleviate memory impairment and metabolic alterations in the disease.
TRANSLATIONAL PSYCHIATRY
(2021)
Review
Neurosciences
Rafaella A. Goncalves, Fernanda G. De Felice
Summary: This article explores the impact of molecules in the peripheral circulation on cognitive function, specifically examining how they can reach the brain and interact with it through various pathways. Understanding the mechanisms of blood-borne molecule transport to the CNS is crucial for developing minimally invasive strategies to deliver therapeutic drugs for neurological disorders.
Article
Behavioral Sciences
Juliana T. S. Fortuna, Matthias Gralle, Danielle Beckman, Fernanda S. Neves, Luan P. Diniz, Paula S. Frost, Fernanda Barros-Aragao, Luis E. Santos, Rafaella A. Goncalves, Luciana Romao, Daniele C. Zamberlan, Felix A. A. Soares, Carolina Braga, Debora Foguel, Flavia C. A. Gomes, Fernanda G. De Felice, Sergio T. Ferreira, Julia R. Clarke, Claudia P. Figueiredo
BEHAVIOURAL BRAIN RESEARCH
(2017)