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Journal Neurobiol Dis

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Alternative platelet activation pathways and their role in neurodegenerative diseases.

Paula Ferrer-Raventós, Katrin Beyer,

<h4>Purpose of the review</h4>The study of platelets in the context of neurodegenerative diseases is intensifying, and increasing evidence suggests that platelets may play an important role in the pathogenesis of neurodegenerative disorders. Therefore, we aim to provide a comprehensive overview of the role of platelets and their diverse activation pathways ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105512]

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Heterozygous GBA D490V and ATP13a2 mutations do not exacerbate pathological α-synuclein spread in the prodromal preformed fibrils model in young mice.

Michaela E Johnson, Liza Bergkvist, Lucas Stetzik, Jennifer A Steiner, Lindsay Meyerdirk, Emily Schulz, Emily Wolfrum, Kelvin C Luk, Daniel W Wesson, Dimitri Krainc, Patrik Brundin,

Autophagic dysregulation and lysosomal impairment have been implicated in the pathogenesis of Parkinson's disease, partly due to the identification of mutations in multiple genes involved in these pathways such as GBA, SNCA, ATP13a2 (also known as PARK9), TMEM175 and LRRK2. Mutations resulting in lysosomal dysfunction are proposed to contribute to ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, :105513]

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Therapeutic potential of iron modulating drugs in a mouse model of multiple system atrophy.

Jay J Shukla, Nadia Stefanova, Ashley I Bush, Gawain McColl, David I Finkelstein, Erin J McAllum,

Multiple System Atrophy (MSA) is a rare neurodegenerative synucleinopathy which leads to severe disability followed by death within 6-9 years of symptom onset. There is compelling evidence suggesting that biological trace metals like iron and copper play an important role in synucleinopathies like Parkinson's disease and removing excess brain iron using ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, :105509]

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Second hit hypothesis in dystonia: Dysfunctional cross talk between neuroplasticity and environment?

Lisa Rauschenberger, Susanne Knorr, Antonio Pisani, Mark Hallett, Jens Volkmann, Chi Wang Ip,

One of the great mysteries in dystonia pathophysiology is the role of environmental factors in disease onset and development. Progress has been made in defining the genetic components of dystonic syndromes, still the mechanisms behind the discrepant relationship between dystonic genotype and phenotype remain largely unclear. Within this review, the ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105511]

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Formalin RT-QuIC assay detects prion-seeding activity in formalin-fixed brain samples from sporadic Creutzfeldt-Jakob disease patients.

Thi-Thu-Trang Dong, Akio Akagi, Toshiaki Nonaka, Takehiro Nakagaki, Ban Mihara, Masaki Takao, Yasushi Iwasaki, Noriyuki Nishida, Katsuya Satoh,

<h4>Background</h4>The neuropathology of sporadic Creutzfeldt-Jakob disease (sCJD) is usually investigated using formalin-fixed and formic acid-treated brain tissue. However, formalin and formic acid treatment can interfere with immunostaining of abnormal prion protein. Therefore, there is a need for biochemical methods other than immunostaining to investigate abnormal prion protein in postmortem tissue. ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105504]

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Differential involvement of insulin receptor substrate (IRS)-1 and IRS-2 in brain insulin signaling is associated with the effects on amyloid pathology in a mouse model of Alzheimer's disease.

Toshitaka Ochiai, Toshiharu Sano, Takeru Nagayama, Naoto Kubota, Takashi Kadowaki, Tomoko Wakabayashi, Takeshi Iwatsubo,

Insulin signaling has been implicated in the metabolism as well as aging and longevity. Type 2 diabetes mellitus and its core pathology, insulin resistance, has also been implicated in the development of Alzheimer's disease (AD) and amyloid-β deposition in humans. By contrast, genetic ablation of the insulin/IGF-1 signaling (IIS) pathway ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, :105510]

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Obstructive sleep apneas naturally occur in mice during REM sleep and are highly prevalent in a mouse model of Down syndrome.

Maria Lavinia Bartolucci, Chiara Berteotti, Sara Alvente, Stefano Bastianini, Sandra Guidi, Viviana Lo Martire, Gabriele Matteoli, Alessandro Silvani, Fiorenza Stagni, Marcello Bosi, Giulio Alessandri-Bonetti, Renata Bartesaghi, Giovanna Zoccoli,

<h4>Study objectives</h4>The use of mouse models in sleep apnea study is limited by the belief that central (CSA) but not obstructive sleep apneas (OSA) occur in rodents. We aimed to develop a protocol to investigate the presence of OSAs in wild-type mice and, then, to apply it to a validated ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105508]

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A novel glucosylceramide synthase inhibitor attenuates alpha synuclein pathology and lysosomal dysfunction in preclinical models of synucleinopathy.

Mali Cosden, Sarah Jinn, Lihang Yao, Cheryl A Gretzula, Monika Kandebo, Dawn Toolan, Nathan G Hatcher, Lei Ma, Wei Lemaire, Gregory C Adam, Christine Burlein, Christina Minnick, Rose Flick, Marla L Watt, James Mulhearn, Mark Fraley, Robert E Drolet, Jacob N Marcus, Sean M Smith,

Mutations in the lysosomal enzyme glucocerebrosidase (GCase, GBA1 gene) are the most common genetic risk factor for developing Parkinson's disease (PD). GCase metabolizes the glycosphingolipids glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph). Mutations in GBA1 reduce enzyme activity and the resulting accumulation of glycosphingolipids may contribute to the underlying pathology of PD, ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105507]

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Altered cardiac structure and function is related to seizure frequency in a rat model of chronic acquired temporal lobe epilepsy.

Kim L Powell, Zining Liu, Claire L Curl, Antonia J A Raaijmakers, Pragati Sharma, Emma L Braine, Flavia M Gomes, Shobi Sivathamboo, Vaughan G Macefield, Pablo M Casillas-Espinosa, Nigel C Jones, Lea M Delbridge, Terence J O'Brien,

<h4>Objective</h4>This study aimed to prospectively examine cardiac structure and function in the kainic acid-induced post-status epilepticus (post-KA SE) model of chronic acquired temporal lobe epilepsy (TLE), specifically to examine for changes between the pre-epileptic, early epileptogenesis and the chronic epilepsy stages. We also aimed to examine whether any changes related ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, :105505]

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Amyloid beta acts synergistically as a pro-inflammatory cytokine.

Thomas J LaRocca, Alyssa N Cavalier, Christine M Roberts, Maddie R Lemieux, Pooja Ramesh, Micklaus A Garcia, Christopher D Link,

The amyloid beta (Aβ) peptide is believed to play a central role in Alzheimer's disease (AD), the most common age-related neurodegenerative disorder. However, the natural, evolutionarily selected functions of Aβ are incompletely understood. Here, we report that nanomolar concentrations of Aβ act synergistically with known cytokines to promote pro-inflammatory activation ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105493]

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Elezanumab, a clinical stage human monoclonal antibody that selectively targets repulsive guidance molecule A to promote neuroregeneration and neuroprotection in neuronal injury and demyelination models.

Lili Huang, Emma Fung, Sahana Bose, Andreas Popp, Preethne Böser, John Memmott, Yuliya A Kutskova, Renee Miller, Edit Tarcsa, Corinna Klein, Geertruida M Veldman, Bernhard K Mueller, Yi-Fang Cui,

Repulsive guidance molecule A (RGMa) is a potent inhibitor of axonal growth and a regulator of neuronal cell death. It is up-regulated following neuronal injury and accumulates in chronic neurodegenerative diseases. Neutralizing RGMa has the potential to promote neuroregeneration and neuroprotection. Previously we reported that a rat anti-N terminal RGMa ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105492]

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Genetic ablation of Gpnmb does not alter synuclein-related pathology.

Robert Brendza, Han Lin, Kimberly Stark, Oded Foreman, Janet Tao, Andrew Pierce, Hai Ngu, Kimberle Shen, Amy E Easton, Tushar Bhangale, Diana Chang, Baris Bingol, Brad A Friedman,

The gene GPNMB is known to play roles in phagocytosis and tissue repair, and is upregulated in microglia in many mouse models of neurodegenerative disease as well as in human patients. Nearby genomic variants are associated with both elevated Parkinson's disease (PD) risk and higher expression of this gene, suggesting ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105494]

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Valproic acid suppresses cuprizone-induced hippocampal demyelination and anxiety-like behavior by promoting cholesterol biosynthesis.

Xinjian Zhu, Yuanyuan Yao, Yang Hu, Jiurong Yang, Canyu Zhang, Yuqi He, Aifeng Zhang, Xiufang Liu, Chenchen Zhang, Guangming Gan,

Myelin consists of several layers of tightly compacted membranes that form an insulating sheath around axons. These membranes are highly enriched in cholesterol, which is essential for the myelination process. Proper myelination is crucial for various neurophysiological functions while demyelination may cause CNS disease, such as multiple sclerosis (MS). Recent ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 158:105489]

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The cross-hemispheric nigrostriatal pathway prevents the expression of levodopa-induced dyskinesias.

Vishakh Iyer, Kala Venkiteswaran, Sandip Savaliya, Christopher A Lieu, Erin Handly, Timothy P Gilmour, Allen R Kunselman, Thyagarajan Subramanian,

Parkinson's disease (PD) is a neurodegenerative movement disorder that is routinely treated with levodopa. Unfortunately, long-term dopamine replacement therapy using levodopa leads to levodopa-induced dyskinesias (LID), a significant and disabling side-effect. Clinical findings indicate that LID typically only occurs following the progression of PD motor symptoms from the unilateral (Hoehn ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105491]

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High-fat diet alters stress behavior, inflammatory parameters and gut microbiota in Tg APP mice in a sex-specific manner.

Natalia Yanguas-Casás, Cristina Torres, Andrea Crespo-Castrillo, Sonia Diaz-Pacheco, Kiera Healy, Catherine Stanton, Julie A Chowen, Luis M Garcia-Segura, Maria Angeles Arevalo, John F Cryan, Maria L de Ceballos,

Long-term high-fat diet (HFD) consumption commonly leads to obesity, a major health concern of western societies and a risk factor for Alzheimer's disease (AD). Both conditions present glial activation and inflammation and show sex differences in their incidence, clinical manifestation, and disease course. HFD intake has an important impact on ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105495]

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Altered synaptic glutamate homeostasis contributes to cognitive decline in young APP/PSEN1 mice.

J M Wilcox, D C Consoli, A A Tienda, S Dixit, R A Buchanan, J M May, W P Nobis, F E Harrison,

Non-convulsive epileptiform activity is a common and under-studied comorbidity of Alzheimer's disease that may significantly contribute to onset of clinical symptoms independently of other neuropathological features such as β-amyloid deposition. We used repeated treatment with low dose kainic acid (KA) to trigger sub-threshold epileptiform activity in young (less than 6 months) ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 158:105486]

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Neurophysiological responses of globus pallidus internus during the auditory oddball task in Parkinson's disease.

Frhan I Alanazi, Tameem M Al-Ozzi, Suneil K Kalia, Mojgan Hodaie, Andres M Lozano, Melanie Cohn, William D Hutchison,

Parkinson's disease can be associated with significant cognitive impairment that may lead to dementia. Deep brain stimulation (DBS) of the subthalamic nucleus is an effective therapy for motor symptoms but is associated with cognitive decline. DBS of globus pallidus internus (GPi) poses less risk of cognitive decline so may be ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105490]

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Dual SMN inducing therapies can rescue survival and motor unit function in symptomatic ∆7SMA mice.

Kaitlyn M Kray, Vicki L McGovern, Deepti Chugh, W David Arnold, Arthur H M Burghes,

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by survival motor neuron (SMN) protein deficiency which results in motor neuron loss and muscle atrophy. SMA is caused by a mutation or deletion of the survival motor neuron 1 (SMN1) gene and retention of the nearly identical SMN2 gene. ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105488]

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Constitutive silencing of LRRK2 kinase activity leads to early glucocerebrosidase deregulation and late impairment of autophagy in vivo.

Federica Albanese, Daniela Mercatelli, Luca Finetti, Giulia Lamonaca, Sara Pizzi, Derya R Shimshek, Giovanni Bernacchia, Michele Morari,

Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease. LRRK2 modulates the autophagy-lysosome pathway (ALP), a clearance process subserving the quality control of cellular proteins and organelles. Since dysfunctional ALP might lead to α-synuclein accumulation and, hence, Parkinson's disease, LRRK2 kinase modulation of ALP, its age-dependence and ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105487]

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Rescue of aberrant huntingtin palmitoylation ameliorates mutant huntingtin-induced toxicity.

Fanny L Lemarié, Nicholas S Caron, Shaun S Sanders, Mandi E Schmidt, Yen T N Nguyen, Seunghyun Ko, Xiaohong Xu, Mahmoud A Pouladi, Dale D O Martin, Michael R Hayden,

Huntington disease (HD) is a neurodegenerative disorder caused by a CAG expansion in the HTT gene that codes for an elongated polyglutamine tract in the huntingtin (HTT) protein. HTT is subject to multiple post-translational modifications (PTMs) that regulate its cellular function. Mutating specific PTM sites within mutant HTT (mHTT) in ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 158:105479]

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Small nucleolar RNAs in plasma extracellular vesicles and their discriminatory power as diagnostic biomarkers of Alzheimer's disease.

Nicholas F Fitz, Jiebiao Wang, M Ilyas Kamboh, Radosveta Koldamova, Iliya Lefterov,

The clinical diagnosis of Alzheimer's disease, at its early stage, remains a difficult task. Advanced imaging technologies and laboratory assays to detect Aβ peptides Aβ42 and Aβ40, total and phosphorylated tau in CSF provide a set of biomarkers of developing AD brain pathology and facilitate the diagnostic process. The search ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105481]

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DNAJB6 suppresses alpha-synuclein induced pathology in an animal model of Parkinson's disease.

Sertan Arkan, Mårten Ljungberg, Deniz Kirik, Christian Hansen,

<h4>Background</h4>α-synuclein (α-syn) aggregation can lead to degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) as invariably observed in patients with Parkinson's Disease (PD). The co-chaperone DNAJB6 has previously been found to be expressed at higher levels in PD patients than in control subjects and was also found ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 158:105477]

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Prolonged NCX activation prevents SOD1 accumulation, reduces neuroinflammation, ameliorates motor behavior and prolongs survival in a ALS mouse model.

Serenella Anzilotti, Valeria Valsecchi, Paola Brancaccio, Natascia Guida, Giusy Laudati, Valentina Tedeschi, Tiziana Petrozziello, Francesco Frecentese, Elisa Magli, Brenda Hassler, Ornella Cuomo, Luigi Formisano, Agnese Secondo, Lucio Annunziato, Giuseppe Pignataro,

Imbalance in cellular ionic homeostasis is a hallmark of several neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS). Sodium-calcium exchanger (NCX) is a membrane antiporter that, operating in a bidirectional way, couples the exchange of Ca<sup>2+</sup> and Na <sup>+</sup> ions in neurons and glial cells, thus controlling the intracellular homeostasis of these ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105480]

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Corrigendum to "Long-term seizure dynamics are determined by the nature of seizures and the mutual interactions between them" [Neurobiol. Dis., Volume 154 (2021), Article 105,347].

Jan Kudlacek, Jan Chvojka, Vojtech Kumpost, Barbora Hermanovska, Antonin Posusta, John G R Jefferys, Matias I Maturana, Ondrej Novak, Mark J Cook, Jakub Otahal, Jaroslav Hlinka, Premysl Jiruska,

Neurobiol Dis (Neurobiology of disease)
[2021, :105484]

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Neuroglobin effectively halts vision loss in Harlequin mice at an advanced stage of optic nerve degeneration.

Hélène Cwerman-Thibault, Christophe Lechauve, Vassilissa Malko-Baverel, Sébastien Augustin, Gwendoline Le Guilloux, Élodie Reboussin, Julie Degardin-Chicaud, Manuel Simonutti, Thomas Debeir, Marisol Corral-Debrinski,

Mitochondrial diseases are among the most prevalent groups of inherited neurological disorders, affecting up to 1 in 5000 adults. Despite the progress achieved on the identification of gene mutations causing mitochondrial pathologies, they cannot be cured so far. Harlequin mice, a relevant model of mitochondrial pathology due to apoptosis inducing ... Read more >>

Neurobiol Dis (Neurobiology of disease)
[2021, 159:105483]

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