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Neurobiology of Disease
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5.16
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4663
Papers 4704
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#1Emily M. RochaH-Index: 7
#2Emily M. Rocha (University of Pittsburgh)H-Index: 3
Last.Sean M. SmithH-Index: 10
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Abstract LRRK2 has been implicated in endolysosomal function and likely plays a central role in idiopathic Parkinson's disease (iPD). In iPD, dopaminergic neurons within the substantia nigra are characterized by increased LRRK2 kinase activity, endolysosomal deficits, and accumulation of autophagic vesicles with incompletely degraded substrates, including α-synuclein. Although LRRK2 has been implicated in endolysosomal and autophagic function, it remains unclear whether inhibition of LRRK2 kinas...
#1Carlos Cepeda (Semel Institute for Neuroscience and Human Behavior)H-Index: 54
#2Simon Levinson (Semel Institute for Neuroscience and Human Behavior)
Last.Gary W. Mathern (Semel Institute for Neuroscience and Human Behavior)H-Index: 60
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Abstract Pathological high-frequency oscillations (HFOs), specifically fast ripples (FRs, >250 Hz), are pathognomonic of an active epileptogenic zone. However, the origin of FRs remains unknown. Here we explored the correlation between FRs recorded with intraoperative pre-resection electrocorticography (ECoG) and spontaneous synaptic activity recorded ex vivo from cortical tissue samples resected for the treatment of pharmacoresistant epilepsy. The cohort included 47 children (ages 0.22–9.99 yr)...
#1Yalda Baradaran-Heravi (University of Antwerp)H-Index: 2
#2C. Van Broeckhoven (University of Antwerp)H-Index: 109
Last.Julie van der Zee (University of Antwerp)H-Index: 33
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Abstract Stress granules (SGs) are dynamic membraneless compartments composed out of RNA-binding proteins (RBPs) and RNA molecules that assemble temporarily to allow the cell to cope with cellular stress by stalling mRNA translation and moving synthesis towards cytoprotective proteins. Aberrant SGs have become prime suspects in the nucleation of toxic protein aggregation in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Perturbed SG dynamics appears to be mediated by alte...
#1Eelco van Duinkerken (UvA: University of Amsterdam)
#2Christopher M. Ryan (University of Pittsburgh)H-Index: 55
Abstract Mild to moderate cognitive decrements are a well-known phenomenon associated with diabetes mellitus. In this review, we provide an overview of the cognitive consequences of type 1 and type 2 diabetes based on hallmark studies that follow patients over an extended period of time. In patients with type 1 diabetes, cognitive dysfunction appears soon after diagnosis and can be found in individuals of any age. The magnitude of these effects is generally modest, although their severity is esp...
#1Shi Yu YangH-Index: 29
#2Matthew E. GeggH-Index: 26
Last.Ahv SchapiraH-Index: 98
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Abstract The presence of GBA1 gene mutations increases risk for Parkinson's disease (PD), but the pathogenic mechanisms of GBA1 associated PD remain unknown. Given that impaired α-synuclein turnover is a hallmark of PD pathogenesis and cathepsin D is a key enzyme involved in α-synuclein degradation in neuronal cells, we have examined the relationship of glucocerebrosidase (GCase), cathepsin D and monomeric α-synuclein in human neural crest stem cell derived dopaminergic neurons. We found that no...
#1Aurelie Joly-AmadoH-Index: 6
#2Hayk Davtyan (UCI: University of California, Irvine)H-Index: 14
Last.H.J. Paek (USF: University of South Florida)
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Abstract Abnormal tau hyperphosphorylation and its aggregation into neurofibrillary tangles are a hallmark of tauopathies, neurodegenerative disorders that include Alzheimer's disease (AD). Active and passive Tau-immunotherapy has been proposed as a therapeutic approach to AD with mixed results. One of the limitations of active immunotherapy may be associated with the mediocre immunogenicity of vaccines that are not inducing therapeutically potent titers of antibodies. The aim of this study was ...
#1Noémie Cresto (CNRS: Centre national de la recherche scientifique)
#2Marie-Claude Gaillard (CNRS: Centre national de la recherche scientifique)H-Index: 12
Last.Martine Guillermier (CNRS: Centre national de la recherche scientifique)H-Index: 15
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Abstract The G2019S substitution in the kinase domain of LRRK2 (LRRK2G2019S) is the most prevalent mutation associated with Parkinson's disease (PD). Neurotoxic effects of LRRK2G2019S are thought to result from an increase in its kinase activity as compared to wild type LRRK2. However, it is unclear whether the kinase domain of LRRK2G2019S is sufficient to trigger degeneration or if the full length protein is required. To address this question, we generated constructs corresponding to the C-term...
#1Robyn L. McAdam (Edin.: University of Edinburgh)
#2Andrew Morton (Edin.: University of Edinburgh)H-Index: 4
Last.Karen J. Smillie (Edin.: University of Edinburgh)H-Index: 12
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Abstract Huntington's disease (HD) is caused by CAG repeat expansion within the HTT gene, with the dysfunction and eventual loss of striatal medium spiny neurons a notable feature. Since medium spiny neurons receive high amounts of synaptic input, we hypothesised that this vulnerability originates from an inability to sustain presynaptic performance during intense neuronal activity. To test this hypothesis, primary cultures of either hippocampal or striatal neurons were prepared from either wild...
#1Bo Zhang (WashU: Washington University in St. Louis)H-Index: 25
#2Dongjun Guo (WashU: Washington University in St. Louis)H-Index: 4
Last.Michael Wong (WashU: Washington University in St. Louis)H-Index: 35
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Abstract Tuberous sclerosis complex (TSC) is a genetic disease related to hyperactivation of the mechanistic target of rapamycin (mTOR) pathway and manifested by neurological symptoms, such as epilepsy and sleep disorders. The pathophysiology of sleep dysfunction is poorly understood and is likely multifactorial, but may involve intrinsic biological regulators in the brain. Here, we characterized a mouse model of sleep disorders in TSC and investigated mechanisms of sleep dysfunction in this con...
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