Microglia are innate immune cells of the brain that perform phagocytic and inflammatory functions in disease conditions. Transcriptomic studies of acutely-isolated microglia have provided novel insights into t...
Authors: Srikant Rangaraju, Eric B. Dammer, Syed Ali Raza, Tianwen Gao, Hailian Xiao, Ranjita Betarbet, Duc M. Duong, James A. Webster, Chadwick M. Hales, James J. Lah, Allan I. Levey and Nicholas T. Seyfried
Type 2 diabetes (T2D) is a recognized risk factor for the development of cognitive impairment (CI) and/or dementia, although the exact nature of the molecular pathology of T2D-associated CI remains obscure. On...
Authors: Cesar L. Moreno, Lucio Della Guardia, Valeria Shnyder, Maitane Ortiz-Virumbrales, Ilya Kruglikov, Bin Zhang, Eric E. Schadt, Rudolph E. Tanzi, Scott Noggle, Christoph Buettner and Sam Gandy
Loss of function mutations in progranulin (GRN) are a major cause of frontotemporal dementia (FTD). Progranulin is a secreted glycoprotein that localizes to lysosomes and is critical for proper lysosomal function...
Authors: Andrew E. Arrant, Alexandra M. Nicholson, Xiaolai Zhou, Rosa Rademakers and Erik D. Roberson
Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder caused by expansion of the polyglutamine repeat in the ataxin-3 protein. Expression of mutant ataxin-3 is known to result in tra...
Authors: Lodewijk J. A. Toonen, Maurice Overzier, Melvin M. Evers, Leticia G. Leon, Sander A. J. van der Zeeuw, Hailiang Mei, Szymon M. Kielbasa, Jelle J. Goeman, Kristina M. Hettne, Olafur Th. Magnusson, Marion Poirel, Alexandre Seyer, Peter A. C. ‘t Hoen and Willeke M. C. van Roon-Mom
Paraspeckles are subnuclear bodies assembled on a long non-coding RNA (lncRNA) NEAT1. Their enhanced formation in spinal neurons of sporadic amyotrophic lateral sclerosis (ALS) patients has been reported but u...
Authors: Tatyana A. Shelkovnikova, Michail S. Kukharsky, Haiyan An, Pasquale Dimasi, Svetlana Alexeeva, Osman Shabir, Paul R. Heath and Vladimir L. Buchman
The R47H variant of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) confers greatly increased risk for Alzheimer’s disease (AD), reflective of a central role for myeloid cells in neurodegeneration. Un...
Authors: Paul J. Cheng-Hathaway, Erin G. Reed-Geaghan, Taylor R. Jay, Brad T. Casali, Shane M. Bemiller, Shweta S. Puntambekar, Victoria E. von Saucken, Roxanne Y. Williams, J. Colleen Karlo, Miguel Moutinho, Guixiang Xu, Richard M. Ransohoff, Bruce T. Lamb and Gary E. Landreth
Several molecular pathways are currently being targeted in attempts to develop disease-modifying therapies to slow down neurodegeneration in Parkinson’s disease. Failure of cellular energy metabolism has long ...
Authors: Emmanuel Quansah, Wouter Peelaerts, J. William Langston, David K. Simon, Jerry Colca and Patrik Brundin
Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there...
Authors: Eduarda G Z Centeno, Helena Cimarosti and Angela Bithell
Administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases regulatory T cell (Treg) number and function with control of neuroinflammation and neuronal protection in the 1-methyl-4-ph...
Authors: Charles R. Schutt, Howard E. Gendelman and R. Lee Mosley
Huntington Disease (HD) is an incurable autosomal dominant neurodegenerative disorder driven by an expansion repeat giving rise to the mutant huntingtin protein (mHtt), which is known to disrupt a multitude of...
Authors: Rebecca Kusko, Jennifer Dreymann, Jermaine Ross, Yoonjeong Cha, Renan Escalante-Chong, Marta Garcia-Miralles, Liang Juin Tan, Michael E. Burczynski, Ben Zeskind, Daphna Laifenfeld, Mahmoud Pouladi, Michal Geva, Iris Grossman and Michael R. Hayden
Disease-associated-microglia (DAM) represent transcriptionally-distinct and neurodegeneration-specific microglial profiles with unclear significance in Alzheimer’s disease (AD). An understanding of heterogenei...
Authors: Srikant Rangaraju, Eric B. Dammer, Syed Ali Raza, Priyadharshini Rathakrishnan, Hailian Xiao, Tianwen Gao, Duc M. Duong, Michael W. Pennington, James J. Lah, Nicholas T. Seyfried and Allan I. Levey
Prior studies in C. elegans demonstrated that the expression of aggregation-prone polyglutamine proteins in muscle wall cells compromised the folding of co-expressed temperature-sensitive proteins, prompting inte...
Authors: Michael C. Pace, Guilian Xu, Susan Fromholt, John Howard, Benoit I. Giasson, Jada Lewis and David R. Borchelt
Extracellular aggregation of the amyloid-β (Aβ) peptide into toxic multimers is a key event in Alzheimer’s disease (AD) pathogenesis. Aβ aggregation is concentration-dependent, with higher concentrations of Aβ...
Authors: Jane C. Hettinger, Hyo Lee, Guojun Bu, David M. Holtzman and John R. Cirrito
Intraneuronal α-synuclein (α-Syn) aggregates known as Lewy bodies (LBs) and the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) are the pathological hallmarks of Parkinson’s disease (...
Authors: Norihito Uemura, Hisashi Yagi, Maiko T. Uemura, Yusuke Hatanaka, Hodaka Yamakado and Ryosuke Takahashi
Neurodegenerative diseases are a growing burden in modern society, thus crucially calling for the development of accurate diagnostic strategies. These diseases are currently incurable, a fact which has been at...
Authors: Maria Paraskevaidi, Pierre L. Martin-Hirsch and Francis L. Martin
Retinitis pigmentosa (RP) is a group of hereditary retinal neurodegenerative conditions characterized by primary dysfunction and death of photoreceptor cells, resulting in visual loss and, eventually, blindnes...
Authors: Alonso Sánchez-Cruz, Beatriz Villarejo-Zori, Miguel Marchena, Josefa Zaldivar-Díez, Valle Palomo, Carmen Gil, Ignacio Lizasoain, Pedro de la Villa, Ana Martínez, Enrique J. de la Rosa and Catalina Hernández-Sánchez
Proteolytic processing of the prion protein (PrPC) by endogenous proteases generates bioactive membrane-bound and soluble fragments which may help to explain the pleiotropic roles of this protein in the nervous s...
Authors: Luise Linsenmeier, Behnam Mohammadi, Sebastian Wetzel, Berta Puig, Walker S. Jackson, Alexander Hartmann, Keiji Uchiyama, Suehiro Sakaguchi, Kristina Endres, Jörg Tatzelt, Paul Saftig, Markus Glatzel and Hermann C. Altmeppen
Traumatic Brain Injury (TBI) is a major cause of disability and mortality, to which there is currently no comprehensive treatment. Blood Brain Barrier (BBB) dysfunction is well documented in human TBI patients...
Authors: Bevan S. Main, Sonia Villapol, Stephanie S. Sloley, David J. Barton, Maia Parsadanian, Chinyere Agbaegbu, Kathryn Stefos, Mondona S. McCann, Patricia M. Washington, Olga C. Rodriguez and Mark P. Burns
Aging is the strongest risk factor for neurodegenerative diseases and extended age results in neuronal degeneration and functional decline in the visual system. Among many contributing factors to age-related d...
Authors: Todd McLaughlin, Marek Falkowski, Jae Whan Park, Stephen Keegan, Michael Elliott, Joshua J. Wang and Sarah X. Zhang
TREM2 is an innate immune receptor specifically expressed in microglia. Coding variations in TREM2 have been reported to increase the risk for Alzheimer’s disease (AD) and other neurodegenerative diseases. Whi...
Authors: Li Zhong, Zongqi Wang, Daxin Wang, Zhe Wang, Yuka A. Martens, Linbei Wu, Ying Xu, Kai Wang, Jianguo Li, Ruizhi Huang, Dan Can, Huaxi Xu, Guojun Bu and Xiao-Fen Chen
Metabolically-obese, normal-weight (MONW) individuals are not obese in terms of weight and height but have a number of obesity-related features (e.g. greater visceral adiposity, insulin resistance, and increas...
Authors: Margalida Cifre, Andreu Palou and Paula Oliver
We have evaluated the efficacy of targeting the toxic, oligomeric form of tau protein by passive immunotherapy in a mouse model of synucleinopathy. Parkinson’s disease and Lewy body dementia are two of the mos...
Authors: Julia E. Gerson, Kathleen M. Farmer, Natalie Henson, Diana L. Castillo-Carranza, Mariana Carretero Murillo, Urmi Sengupta, Alan Barrett and Rakez Kayed
Degeneration of cone photoreceptors leads to loss of vision in patients suffering from age-related macular degeneration (AMD) and other cone dystrophies. Evidence, such as choroidal ischemia and decreased chor...
Authors: Maya Barben, Christian Schori, Marijana Samardzija and Christian Grimm
Besides the two main classical features of amyloid beta aggregation and tau-containing neurofibrillary tangle deposition, neuroinflammation plays an important yet unclear role in the pathophysiology of Alzheim...
Authors: Justyna Sosna, Stephan Philipp, Ricardo Albay III, Jorge Mauricio Reyes-Ruiz, David Baglietto-Vargas, Frank M. LaFerla and Charles G. Glabe
Dynactin p150Glued, the largest subunit of the dynactin macromolecular complex, binds to both microtubules and tubulin dimers through the N-terminal cytoskeleton-associated protein and glycine-rich (CAP-Gly) and ...
Authors: Jia Yu, Chen Lai, Hoon Shim, Chengsong Xie, Lixin Sun, Cai-Xia Long, Jinhui Ding, Yan Li and Huaibin Cai
α-Synuclein is a presynaptic protein abundant in the cytoplasmic compartment of neurons, whereas its presence in the extracellular space has also been observed under physiological conditions. Extracellular α-s...
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial and sporadic Parkinson’s disease (PD). Elevated kinase activity is associated with LRRK2 toxicity, but the substrates that m...
Authors: Ga Ram Jeong, Eun-Hae Jang, Jae Ryul Bae, Soyoung Jun, Ho Chul Kang, Chi-Hu Park, Joo-Ho Shin, Yukio Yamamoto, Keiko Tanaka-Yamamoto, Valina L. Dawson, Ted M. Dawson, Eun-Mi Hur and Byoung Dae Lee
Progressive neuron loss in the frontal and temporal lobes of the cerebral cortex typifies frontotemporal lobar degeneration (FTLD). FTLD sub types are classified on the basis of neuronal aggregated protein dep...
Authors: Laura M. Taylor, Pamela J. McMillan, Nicole F. Liachko, Timothy J. Strovas, Bernardino Ghetti, Thomas D. Bird, C. Dirk Keene and Brian C. Kraemer
β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in the production of amyloid beta (Aβ), the toxic peptide that accumulates in the brains of Alzheimer’s disease (AD) patie...
Authors: WonHee Kim, Liang Ma, Selene Lomoio, Rachel Willen, Sylvia Lombardo, Jinghui Dong, Philip G. Haydon and Giuseppina Tesco
Mitochondria are the organelles responsible for energy metabolism and have a direct impact on neuronal function and survival. Mitochondrial abnormalities have been well characterized in Alzheimer Disease (AD)....
Authors: Sirui Jiang, Priya Nandy, Wenzhang Wang, Xiaopin Ma, Jeffrey Hsia, Chunyu Wang, Zhenlian Wang, Mengyue Niu, Sandra L. Siedlak, Sandy Torres, Hisashi Fujioka, Ying Xu, Hyoung-gon Lee, George Perry, Jun Liu and Xiongwei Zhu
Spinocerebellar ataxia 17 (SCA17) belongs to the family of neurodegenerative diseases caused by polyglutamine (polyQ) expansion. In SCA17, polyQ expansion occurs in the TATA box binding protein (TBP) and leads...
Authors: Jifeng Guo, Yiting Cui, Qiong Liu, Yang Yang, Yujing Li, Ling Weng, Beisha Tang, Peng Jin, Xiao-Jiang Li, Su Yang and Shihua Li
Mutations in LRRK2 are a common genetic cause of Parkinson’s disease (PD). LRRK2 interacts with and phosphorylates a subset of Rab proteins including Rab8a, a protein which has been implicated in various centr...
Authors: Jesús Madero-Pérez, Elena Fdez, Belén Fernández, Antonio J. Lara Ordóñez, Marian Blanca Ramírez, Patricia Gómez-Suaga, Dieter Waschbüsch, Evy Lobbestael, Veerle Baekelandt, Angus C. Nairn, Javier Ruiz-Martínez, Ana Aiastui, Adolfo López de Munain, Pawel Lis, Thomas Comptdaer, Jean-Marc Taymans…
Alzheimer’s disease (AD), the most common neurodegenerative disorder, is characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles. To understand the pathologic...
Authors: Dong Kyu Kim, Joonho Park, Dohyun Han, Jinhee Yang, Ahbin Kim, Jongmin Woo, Youngsoo Kim and Inhee Mook-Jung
Mutations in glucocerebrosidase (GBA) cause Gaucher disease (GD) and increase the risk of developing Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB). Since both genetic and environmental factors c...
Authors: Seung Pil Yun, Donghoon Kim, Sangjune Kim, SangMin Kim, Senthilkumar S. Karuppagounder, Seung-Hwan Kwon, Saebom Lee, Tae-In Kam, Suhyun Lee, Sangwoo Ham, Jae Hong Park, Valina L. Dawson, Ted M. Dawson, Yunjong Lee and Han Seok Ko
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders that share genetic risk factors and pathological hallmarks. Intriguingly, these shared factors result in a ...
Authors: Zhiqiang Deng, Patricia Sheehan, Shi Chen and Zhenyu Yue
Alzheimer’s disease (AD) is behaviorally identified by progressive memory impairment and pathologically characterized by the triad of β-amyloid plaques, neurofibrillary tangles, and neurodegeneration. Genetic ...
The microtubule-associated protein Tau plays a role in neurodegeneration as well as neurogenesis. Previous work has shown that the expression of the pro-aggregant mutant Tau repeat domain causes strong aggrega...
Authors: Maria Joseph, Marta Anglada-Huguet, Katharina Paesler, Eckhard Mandelkow and Eva-Maria Mandelkow
Tau is a microtubule-binding protein, which is subject to various post-translational modifications (PTMs) including phosphorylation, methylation, acetylation, glycosylation, nitration, sumoylation and truncati...
Authors: Ebru Ercan, Sameh Eid, Christian Weber, Alexandra Kowalski, Maria Bichmann, Annika Behrendt, Frank Matthes, Sybille Krauss, Peter Reinhardt, Simone Fulle and Dagmar E. Ehrnhoefer
Alzheimer’s disease (AD) is characterized by amyloid deposition, tangle formation as well as synapse loss. Synaptic abnormalities occur early in the pathogenesis of AD. Identifying early synaptic abnormalities...
Authors: Yang Bai, Miao Li, Yanmei Zhou, Lei Ma, Qian Qiao, Wanling Hu, Wei Li, Zachary Patrick Wills and Wen-Biao Gan
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative condition where loss of motor neurons within the brain and spinal cord leads to muscle atrophy, weakness, paralysis and ultimately...
Authors: Yuri Ciervo, Ke Ning, Xu Jun, Pamela J. Shaw and Richard J. Mead
Parkinson’s disease (PD) is a progressive movement neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Oxidative stress, a condition that occurs due t...
Authors: Karim Belarbi, Elodie Cuvelier, Alain Destée, Bernard Gressier and Marie-Christine Chartier-Harlin
YKL-40 (also known as Chitinase 3-like 1) is a glycoprotein produced by inflammatory, cancer and stem cells. Its physiological role is not completely understood but YKL-40 is elevated in the brain and cerebros...
Authors: Franc Llorens, Katrin Thüne, Waqas Tahir, Eirini Kanata, Daniela Diaz-Lucena, Konstantinos Xanthopoulos, Eleni Kovatsi, Catharina Pleschka, Paula Garcia-Esparcia, Matthias Schmitz, Duru Ozbay, Susana Correia, Ângela Correia, Ira Milosevic, Olivier Andréoletti, Natalia Fernández-Borges…
Oligodendrocytes (OLs) and myelin are critical for normal brain function and have been implicated in neurodegeneration. Several lines of evidence including neuroimaging and neuropathological data suggest that ...
Authors: Andrew T. McKenzie, Sarah Moyon, Minghui Wang, Igor Katsyv, Won-Min Song, Xianxiao Zhou, Eric B. Dammer, Duc M. Duong, Joshua Aaker, Yongzhong Zhao, Noam Beckmann, Pei Wang, Jun Zhu, James J. Lah, Nicholas T. Seyfried, Allan I. Levey…
Metabolic perturbations and slower renewal of cellular components associated with aging increase the risk of Parkinson’s disease (PD). Declining activity of AMPK, a critical cellular energy sensor, may therefo...
Authors: Wojciech Bobela, Sameer Nazeeruddin, Graham Knott, Patrick Aebischer and Bernard L. Schneider
Genome wide association studies have identified microtubule associated protein tau (MAPT) H1 haplotype single nucleotide polymorphisms (SNPs) as leading common risk variants for Parkinson’s disease, progressive s...
Authors: Mang Ching Lai, Anne-Laure Bechy, Franziska Denk, Emma Collins, Maria Gavriliouk, Judith B. Zaugg, Brent J. Ryan, Richard Wade-Martins and Tara M. Caffrey
Neuronal degeneration is a common mechanism of many neurological diseases including Parkinson’s disease (PD), Alzheimer’s disease (AD), and Multiple Sclerosis (MS). While AD and PD are classical neurodegenerat...
Authors: Annika Sommer, Beate Winner and Iryna Prots
Neurons are highly polarized cells consisting of three distinct functional domains: the cell body (and associated dendrites), the axon and the synapse. Previously, it was believed that the clinical phenotypes ...
Authors: Laura C. Graham, Samantha L. Eaton, Paula J. Brunton, Abdelmadjid Atrih, Colin Smith, Douglas J. Lamont, Thomas H. Gillingwater, Giuseppa Pennetta, Paul Skehel and Thomas M. Wishart
The objective of this study was to investigate cellular bioenergetics in primary skin fibroblasts derived from patients with amyotrophic lateral sclerosis (ALS) and to determine if they can be used as classifi...
Authors: Csaba Konrad, Hibiki Kawamata, Kirsten G. Bredvik, Andrea J. Arreguin, Steven A. Cajamarca, Jonathan C. Hupf, John M. Ravits, Timothy M. Miller, Nicholas J. Maragakis, Chadwick M. Hales, Jonathan D. Glass, Steven Gross, Hiroshi Mitsumoto and Giovanni Manfredi
The homeostasis of iron is vital to human health, and iron dyshomeostasis can lead to various disorders. Iron homeostasis is maintained by iron regulatory proteins (IRP1 and IRP2) and the iron-responsive eleme...
