Articles

Transient IKK2 activation in astrocytes initiates selective non-cell-autonomous neurodegeneration

Neuroinflammation is associated with a wide range of neurodegenerative disorders, however the specific contribution to individual disease pathogenesis and selective neuronal cell death is not well understood. ...

Authors: Michael Lattke, Stephanie N. Reichel, Alexander Magnutzki, Alireza Abaei, Volker Rasche, Paul Walther, Dinis P. Calado, Boris Ferger, Thomas Wirth and Bernd Baumann

Dynamic presenilin 1 and synaptotagmin 1 interaction modulates exocytosis and amyloid β production

Alzheimer’s disease (AD)-linked protein, presenilin 1 (PS1), is present at the synapse, and the knock-out of presenilin in mice leads to synaptic dysfunction. On the other hand, synaptic activity was shown to ...

Authors: Katarzyna Marta Zoltowska, Masato Maesako, Iryna Lushnikova, Shuko Takeda, Laura J. Keller, Galina Skibo, Bradley T. Hyman and Oksana Berezovska

Gene-environment interaction between lead and Apolipoprotein E4 causes cognitive behavior deficits in mice

Alzheimer’s disease (AD) is characterized by progressive cognitive decline and memory loss. Environmental factors and gene-environment interactions (GXE) may increase AD risk, accelerate cognitive decline, and...

Authors: Anna K. Engstrom, Jessica M. Snyder, Nobuyo Maeda and Zhengui Xia

Tdp-43 cryptic exons are highly variable between cell types

TDP-43 proteinopathy is a prominent pathological feature that occurs in a number of human diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and inclusion body myositis (IBM...

Authors: Yun Ha Jeong, Jonathan P. Ling, Sophie Z. Lin, Aneesh N. Donde, Kerstin E. Braunstein, Elisa Majounie, Bryan J. Traynor, Katherine D. LaClair, Thomas E. Lloyd and Philip C. Wong

APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice

APOE genotype is the foremost genetic factor modulating β-amyloid (Aβ) deposition and risk of sporadic Alzheimer’s disease (AD). Here we investigated how APOE genotype influences respo...

Authors: Joanna E Pankiewicz, Jairo Baquero-Buitrago, Sandrine Sanchez, Jennifer Lopez-Contreras, Jungsu Kim, Patrick M. Sullivan, David M. Holtzman and Martin J. Sadowski

Therapeutic potential of autophagy-enhancing agents in Parkinson’s disease

Converging evidence from genetic, pathological and experimental studies have increasingly suggested an important role for autophagy impairment in Parkinson’s Disease (PD). Genetic studies have identified mutat...

Authors: Tim E. Moors, Jeroen J. M. Hoozemans, Angela Ingrassia, Tommaso Beccari, Lucilla Parnetti, Marie-Christine Chartier-Harlin and Wilma D. J. van de Berg

The SH-SY5Y cell line in Parkinson’s disease research: a systematic review

Parkinson’s disease (PD) is a devastating and highly prevalent neurodegenerative disease for which only symptomatic treatment is available. In order to develop a truly effective disease-modifying therapy, impr...

Authors: Helena Xicoy, Bé Wieringa and Gerard J.M. Martens

Pathogenic LRRK2 variants are gain-of-function mutations that enhance LRRK2-mediated repression of β-catenin signaling

LRRK2 mutations and risk variants increase susceptibility to inherited and idiopathic Parkinson’s disease, while recent studies have identified potential protective variants. This, and...

Authors: Daniel C. Berwick, Behzad Javaheri, Andrea Wetzel, Mark Hopkinson, Jonathon Nixon-Abell, Simone Grannò, Andrew A. Pitsillides and Kirsten Harvey

GDE2 is essential for neuronal survival in the postnatal mammalian spinal cord

Glycerophosphodiester phosphodiesterase 2 (GDE2) is a six-transmembrane protein that cleaves glycosylphosphatidylinositol (GPI) anchors to regulate GPI-anchored protein activity at the cell surface. In the dev...

Authors: Clinton Cave, Sungjin Park, Marianeli Rodriguez, Mai Nakamura, Ahmet Hoke, Mikhail Pletnikov and Shanthini Sockanathan

NADPH oxidase in brain injury and neurodegenerative disorders

Oxidative stress is a common denominator in the pathology of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and multiple scle...

Authors: Merry W. Ma, Jing Wang, Quanguang Zhang, Ruimin Wang, Krishnan M. Dhandapani, Ratna K. Vadlamudi and Darrell W. Brann

Glycine-alanine dipeptide repeat protein contributes to toxicity in a zebrafish model of C9orf72 associated neurodegeneration

The most frequent genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) is the expansion of a GGGGCC hexanucleotide repeat in a non-coding region of the chromosome 9...

Authors: Yu Ohki, Andrea Wenninger-Weinzierl, Alexander Hruscha, Kazuhide Asakawa, Koichi Kawakami, Christian Haass, Dieter Edbauer and Bettina Schmid

The release and trans-synaptic transmission of Tau via exosomes

Tau pathology in AD spreads in a hierarchical pattern, whereby it first appears in the entorhinal cortex, then spreads to the hippocampus and later to the surrounding areas. Based on this sequential appearance...

Authors: Yipeng Wang, Varun Balaji, Senthilvelrajan Kaniyappan, Lars Krüger, Stephan Irsen, Katharina Tepper, RamReddy Chandupatla, Walter Maetzler, Anja Schneider, Eckhard Mandelkow and Eva-Maria Mandelkow

Erratum to: The impact of glutamine supplementation on the symptoms of ataxia-telangiectasia: a preclinical assessment

Authors: Jianmin Chen, Yanping Chen, Graham Vail, Heiman Chow, Yang Zhang, Lauren Louie, Jiali Li, Ronald P. Hart, Mark R. Plummer and Karl Herrup

Erratum to: Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation

Authors: Thiyagaragan M. Achariyar, Baoman Li, Weiguo Peng, Philip B. Verghese, Yang Shi, Evan McConnell, Abdellatif Benraiss, Tristan Kasper, Wei Song, Takahiro Takano, David M. Holtzman, Maiken Nedergaard and Rashid Deane

Immunochemical characterization on pathological oligomers of mutant Cu/Zn-superoxide dismutase in amyotrophic lateral sclerosis

Dominant mutations in Cu/Zn-superoxide dismutase (SOD1) gene cause a familial form of amyotrophic lateral sclerosis (SOD1-ALS) with accumulation of misfolded SOD1 proteins as intracellular inclusions in spinal mo...

Authors: Eiichi Tokuda, Itsuki Anzai, Takao Nomura, Keisuke Toichi, Masahiko Watanabe, Shinji Ohara, Seiji Watanabe, Koji Yamanaka, Yuta Morisaki, Hidemi Misawa and Yoshiaki Furukawa

Inflammatory pre-conditioning restricts the seeded induction of α-synuclein pathology in wild type mice

Cell-to-cell transmission of α-synuclein (αSyn) is hypothesized to play an important role in disease progression in synucleinopathies. This process involves cellular uptake of extracellular amyloidogenic αSyn ...

Authors: Emily J. Koller, Mieu M. T. Brooks, Todd E. Golde, Benoit I. Giasson and Paramita Chakrabarty

ULK1-mediated phosphorylation of ATG14 promotes autophagy and is impaired in Huntington’s disease models

Autophagy is a bulk degradation pathway for long-lived proteins, protein aggregates, and damaged organelles. ULK1 protein kinase and Vps34 lipid kinase are two key autophagy regulators that are critical for au...

Authors: Mitchell S. Wold, Junghyun Lim, Véronik Lachance, Zhiqiang Deng and Zhenyu Yue

3D culture models of Alzheimer’s disease: a road map to a “cure-in-a-dish”

Alzheimer’s disease (AD) transgenic mice have been used as a standard AD model for basic mechanistic studies and drug discovery. These mouse models showed symbolic AD pathologies including β-amyloid (Aβ) plaqu...

Authors: Se Hoon Choi, Young Hye Kim, Luisa Quinti, Rudolph E. Tanzi and Doo Yeon Kim

Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation

Apolipoprotein E (apoE) is a major carrier of cholesterol and essential for synaptic plasticity. In brain, it’s expressed by many cells but highly expressed by the choroid plexus and the predominant apolipopro...

Authors: Thiyagaragan M. Achariyar, Baoman Li, Weiguo Peng, Philip B. Verghese, Yang Shi, Evan McConnell, Abdellatif Benraiss, Tristan Kasper, Wei Song, Takahiro Takano, David M. Holtzman, Maiken Nedergaard and Rashid Deane

LRRK2 at the interface of autophagosomes, endosomes and lysosomes

Over the past 20 years, substantial progress has been made in identifying the underlying genetics of Parkinson’s disease (PD). Of the known genes, LRRK2 is a major genetic contributor to PD. However, the exact...

Authors: Dorien A. Roosen and Mark R. Cookson

Expression and processing analyses of wild type and p.R47H TREM2 variant in Alzheimer’s disease brains

Genetic analyses showed that the triggering receptor expressed in myeloid cells 2 (TREM2) p.R47H variant increases the risk for Alzheimer’s disease (AD). The question of whether the p.R47H mutation affects exp...

Authors: Li Ma, Mariet Allen, Nobutaka Sakae, Nilufer Ertekin-Taner, Neill R. Graff-Radford, Dennis W. Dickson, Steven G. Younkin and Daniel Sevlever

Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

Insulin resistance is the major pathogenesis underlying type 2 diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer’s disease (AD). Increasing evidence suggests that insulin resistance pl...

Authors: Roy Chun-Laam Ng, On-Yin Cheng, Min Jian, Jason Shing-Cheong Kwan, Philip Wing-Lok Ho, Kenneth King-Yip Cheng, Patrick Ka Kit Yeung, Lena Lei Zhou, Ruby Lai-Chong Hoo, Sookja Kim Chung, Aimin Xu, Karen Siu-Ling. Lam and Koon Ho Chan

Role of cytochrome c in α-synuclein radical formation: implications of α-synuclein in neuronal death in Maneb- and paraquat-induced model of Parkinson’s disease

The pathological features of Parkinson’s disease (PD) include an abnormal accumulation of α-synuclein in the surviving dopaminergic neurons. Though PD is multifactorial, several epidemiological reports show an...

Authors: Ashutosh Kumar, Douglas Ganini and Ronald P. Mason

Progranulin promotes peripheral nerve regeneration and reinnervation: role of notch signaling

Peripheral nerve injury is a frequent cause of lasting motor deficits and chronic pain. Although peripheral nerves are capable of regrowth they often fail to re-innervate target tissues.

Authors: Christine Altmann, Verica Vasic, Stefanie Hardt, Juliana Heidler, Annett Häussler, Ilka Wittig, Mirko H. H. Schmidt and Irmgard Tegeder

Spinal cord injury induces astroglial conversion towards neuronal lineage

Neurons have intrinsic capability to regenerate after lesion, though not spontaneously. Spinal cord injury (SCI) causes permanent neurological impairments partly due to formation of a glial scar that is compos...

Authors: Harun Najib Noristani, Jean Charles Sabourin, Hassan Boukhaddaoui, Emilie Chan-Seng, Yannick Nicolas Gerber and Florence Evelyne Perrin

Seizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons

The protease BACE1 (beta-site APP cleaving enzyme) is a major drug target in Alzheimer’s disease. However, BACE1 therapeutic inhibition may cause unwanted adverse effects due to its additional functions in the...

Authors: Martina Pigoni, Johanna Wanngren, Peer-Hendrik Kuhn, Kathryn M. Munro, Jenny M. Gunnersen, Hiroshi Takeshima, Regina Feederle, Iryna Voytyuk, Bart De Strooper, Mikail D. Levasseur, Brian J. Hrupka, Stephan A. Müller and Stefan F. Lichtenthaler

Cerebrospinal fluid Presenilin-1 increases at asymptomatic stage in genetically determined Alzheimer’s disease

Presenilin-1 (PS1), the active component of the intramembrane γ-secretase complex, can be detected as soluble heteromeric aggregates in cerebrospinal fluid (CSF). The aim of this study was to examine the diffe...

Authors: Aitana Sogorb-Esteve, María-Salud García-Ayllón, Juan Fortea, Raquel Sánchez-Valle, Alberto Lleó, José-Luis Molinuevo and Javier Sáez-Valero

No diurnal variation of classical and candidate biomarkers of Alzheimer’s disease in CSF

Cerebrospinal fluid (CSF) biomarkers have gained increasing importance in the diagnostic work-up of Alzheimer’s disease (AD). The core CSF biomarkers related to AD pathology (Aβ42, t-tau and p-tau) are current...

Authors: Claudia Cicognola, Davide Chiasserini, Paolo Eusebi, Ulf Andreasson, Hugo Vanderstichele, Henrik Zetterberg, Lucilla Parnetti and Kaj Blennow

Deimmunization for gene therapy: host matching of synthetic zinc finger constructs enables long-term mutant Huntingtin repression in mice

Synthetic zinc finger (ZF) proteins can be targeted to desired DNA sequences and are useful tools for gene therapy. We recently developed a ZF transcription repressor (ZF-KOX1) able to bind to expanded DNA CAG...

Authors: Carmen Agustín-Pavón, Michal Mielcarek, Mireia Garriga-Canut and Mark Isalan

A Christianson syndrome-linked deletion mutation (∆²⁸⁷ES²⁸⁸) in SLC9A6 disrupts recycling endosomal function and elicits neurodegeneration and cell death

Christianson Syndrome, a recently identified X-linked neurodevelopmental disorder, is caused by mutations in the human gene SLC9A6 encoding the recycling endosomal alkali cation/proton exchanger NHE6. The pati...

Authors: Alina Ilie, Andy Y. L. Gao, Jonathan Reid, Annie Boucher, Cassandra McEwan, Hervé Barrière, Gergely L. Lukacs, R. Anne McKinney and John Orlowski

Affinity of Tau antibodies for solubilized pathological Tau species but not their immunogen or insoluble Tau aggregates predicts in vivo and ex vivo efficacy

A few tau immunotherapies are now in clinical trials with several more likely to be initiated in the near future. A priori, it can be anticipated that an antibody which broadly recognizes various pathological ...

Authors: Erin E. Congdon, Yan Lin, Hameetha B. Rajamohamedsait, Dov B. Shamir, Senthilkumar Krishnaswamy, Wajitha J. Rajamohamedsait, Suhail Rasool, Veronica Gonzalez, Josien Levenga, Jiaping Gu, Charles Hoeffer and Einar M. Sigurdsson

A novel multiplex assay for simultaneous quantification of total and S129 phosphorylated human alpha-synuclein

Alpha-synuclein (asyn) has been shown to play an important role in the neuropathology of Parkinson’s disease (PD). In the diseased brain, classic intraneuronal inclusions called Lewy bodies contain abnormal fo...

Authors: Natalie Landeck, Hélène Hall, Mustafa T. Ardah, Nour K. Majbour, Omar M. A. El-Agnaf, Glenda Halliday and Deniz Kirik

The impact of glutamine supplementation on the symptoms of ataxia-telangiectasia: a preclinical assessment

Our previous studies of Alzheimer’s disease (AD) suggested that glutamine broadly improves cellular readiness to respond to stress and acts as a neuroprotectant both in vitro and in AD mouse models. We now exp...

Authors: Jianmin Chen, Yanping Chen, Graham Vail, Heiman Chow, Yang Zhang, Lauren Louie, Jiali Li, Ronald P. Hart, Mark R. Plummer and Karl Herrup

Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts

Genome-wide association studies have identified BIN1 within the second most significant susceptibility locus in late-onset Alzheimer’s disease (AD). BIN1 undergoes complex alternative splicing to generate multipl...

Authors: Pierre De Rossi, Virginie Buggia-Prévot, Benjamin L. L. Clayton, Jared B. Vasquez, Carson van Sanford, Robert J. Andrew, Ruben Lesnick, Alexandra Botté, Carole Deyts, Someya Salem, Eshaan Rao, Richard C. Rice, Angèle Parent, Satyabrata Kar, Brian Popko, Peter Pytel…

Lentiviral vector-mediated overexpression of mutant ataxin-7 recapitulates SCA7 pathology and promotes accumulation of the FUS/TLS and MBNL1 RNA-binding proteins

We used lentiviral vectors (LVs) to generate a new SCA7 animal model overexpressing a truncated mutant ataxin-7 (MUT ATXN7) fragment in the mouse cerebellum, in order to characterize the specific neuropatholog...

Authors: Sandro Alves, Thibaut Marais, Maria-Grazia Biferi, Denis Furling, Martina Marinello, Khalid El Hachimi, Nathalie Cartier, Merle Ruberg, Giovanni Stevanin, Alexis Brice, Martine Barkats and Annie Sittler

Erratum to: Transmission of α-synucleinopathy from olfactory structures deep into the temporal lobe

Authors: Daniel M. Mason, Negin Nouraei, Deepti B. Pant, Kristin M. Miner, Daniel F. Hutchison, Kelvin C. Luk, John F. Stolz and Rehana K. Leak

ZNStress: a high-throughput drug screening protocol for identification of compounds modulating neuronal stress in the transgenic mutant sod1G93R zebrafish model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease with death on average within 2–3 years of symptom onset. Mutations in superoxide dismutase 1 (SOD1) have been identified to cause ALS. ...

Authors: Alexander McGown, Dame Pamela J. Shaw and Tennore Ramesh

miR-27a and miR-27b regulate autophagic clearance of damaged mitochondria by targeting PTEN-induced putative kinase 1 (PINK1)

Loss-of-function mutations in PINK1 and PARKIN are the most common causes of autosomal recessive Parkinson’s disease (PD). PINK1 is a mitochondrial serine/threonine kinase that plays a critical role in mitophagy,...

Authors: Jaekwang Kim, Fabienne C. Fiesel, Krystal C. Belmonte, Roman Hudec, Wang-Xia Wang, Chaeyoung Kim, Peter T. Nelson, Wolfdieter Springer and Jungsu Kim

IKKβ-mediated inflammatory myeloid cell activation exacerbates experimental autoimmune encephalomyelitis by potentiating Th1/Th17 cell activation and compromising blood brain barrier

The inflammatory myeloid cell activation is one of the hallmarks of experimental autoimmune encephalomyelitis (EAE), yet the in vivo role of the inflammatory myeloid cell activation in EAE has not been clearly...

Authors: Min Jung Lee, So Jin Bing, Jonghee Choi, Minhee Jang, Gihyun Lee, Hyunkyoung Lee, Byung Soo Chang, Youngheun Jee, Sung Joong Lee and Ik-Hyun Cho

Activation of Wnt signaling promotes hippocampal neurogenesis in experimental autoimmune encephalomyelitis

Disease progression in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), as one of its animal models, is characterized by demyelination and neuronal damage in white and gray matter s...

Authors: Reiner Schneider, Barbara Koop, Friederike Schröter, Jason Cline, Jens Ingwersen, Carsten Berndt, Hans-Peter Hartung, Orhan Aktas and Tim Prozorovski

Pim1 inhibition as a novel therapeutic strategy for Alzheimer’s disease

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder worldwide. Clinically, AD is characterized by impairments of memory and cognitive functions. Accumulation of amyloid-β (Aβ) and neurofi...

Authors: Ramon Velazquez, Darren M. Shaw, Antonella Caccamo and Salvatore Oddo

Early-life stress leads to impaired spatial learning and memory in middle-aged ApoE4-TR mice

Apolipoprotein E (ApoE) is a major lipid carrier that supports lipid transport and injury repair in the brain. The APOE ε4 allele is associated with depression, mild cognitive impairment (MCI) and dementia; howev...

Authors: Lan-yan Lin, Jing Zhang, Xiao-man Dai, Nai-an Xiao, Xi-lin Wu, Zhen Wei, Wen-ting Fang, Yuan-gui Zhu and Xiao-chun Chen

Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer’s disease

Alzheimer’s disease (AD) is an incurable and debilitating chronic progressive neurodegenerative disorder which is the leading cause of dementia worldwide. AD is a heterogeneous and multifactorial disorder, his...

Authors: Syed Faraz Kazim and Khalid Iqbal

Transmission of α-synucleinopathy from olfactory structures deep into the temporal lobe

α-synucleinopathy emerges quite early in olfactory structures such as the olfactory bulb and anterior olfactory nucleus (OB/AON) in Parkinson's disease. This may contribute to smell impairments years before th...

Authors: Daniel M. Mason, Negin Nouraei, Deepti B. Pant, Kristin M. Miner, Daniel F. Hutchison, Kelvin C. Luk, John F. Stolz and Rehana K. Leak

Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges

Immunization against amyloid-β (Aβ) peptides deposited in Alzheimer’s disease (AD) has shown considerable therapeutic effect in animal models however, the translation into human Alzheimer’s patients is challen...

Authors: Holger Cynis, Jeffrey L. Frost, Helen Crehan and Cynthia A. Lemere

Acetylated tau destabilizes the cytoskeleton in the axon initial segment and is mislocalized to the somatodendritic compartment

Neurons are highly polarized cells in which asymmetric axonal-dendritic distribution of proteins is crucial for neuronal function. Loss of polarized distribution of the axonal protein tau is an early sign of A...

Authors: Peter Dongmin Sohn, Tara E. Tracy, Hye-In Son, Yungui Zhou, Renata E. P. Leite, Bruce L. Miller, William W. Seeley, Lea T. Grinberg and Li Gan

Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: a novel therapeutic lead to treat frontotemporal dementia

Progranulin (PGRN) is a secreted growth factor important for neuronal survival and may do so, in part, by regulating lysosome homeostasis. Mutations in the PGRN gene (GRN) are a common cause of frontotemporal lob...

Authors: Christopher J. Holler, Georgia Taylor, Zachary T. McEachin, Qiudong Deng, William J. Watkins, Kathryn Hudson, Charles A. Easley, William T. Hu, Chadwick M. Hales, Wilfried Rossoll, Gary J. Bassell and Thomas Kukar

Redundant G_s-coupled serotonin receptors regulate amyloid-β metabolism in vivo

The aggregation of amyloid-β (Aβ) into insoluble plaques is a hallmark pathology of Alzheimer’s disease (AD). Previous work has shown increasing serotonin levels with selective serotonin re-uptake inhibitor (S...

Authors: Jonathan R. Fisher, Clare E. Wallace, Danielle L. Tripoli, Yvette I. Sheline and John R. Cirrito

Synaptophysin depletion and intraneuronal Aβ in organotypic hippocampal slice cultures from huAPP transgenic mice

To date, there are no effective disease-modifying treatments for Alzheimer’s disease (AD). In order to develop new therapeutics for stages where they are most likely to be effective, it is important to identif...

Authors: Claire S. Harwell and Michael P. Coleman

Stathmin 1/2-triggered microtubule loss mediates Golgi fragmentation in mutant SOD1 motor neurons

Pathological Golgi fragmentation represents a constant pre-clinical feature of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) but its molecular mechanisms remain hitherto unclear.

Authors: Sarah Bellouze, Gilbert Baillat, Dorothée Buttigieg, Pierre de la Grange, Catherine Rabouille and Georg Haase