Neurobiology of Disease
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Challenges for taking primary and stem cells into clinical neurotransplantation trials for neurodegenerative disease.
We review the first generations of clinical trials of novel cell therapies applied to a range of neurodegenerative diseases in the context of mechanisms of functional efficacy. This in turn helps to determine the best strategies to be adopted and the potential chances for success in developing new c...
Managing your patent assets.
I have provided "real world" examples in the form of case studies to support my advice. My goal is to arm you with sufficient knowledge so as to enable you to devise a patent strategy that suits your company's business and scientific needs. © 2013 Elsevier Inc. All rights reserved....
DJ-1 facilitates the interaction between STAT1 and its phosphatase, SHP-1, in brain microglia and astrocytes: A novel anti-inflammatory func...
We demonstrate a novel mechanism by which DJ-1 (PARK7), an early onset autosomal-recessive PD gene, negatively regulates inflammatory responses of astrocytes and microglia by facilitating the interaction between STAT1 and its phosphatase, SHP-1 (Src-homology 2-domain containing protein tyrosine phos...
Dynein mutations associated with hereditary motor neuropathies impair mitochondrial morphology and function with age.
We show that mouse fibroblasts bearing heterozygous or homozygous point mutation in Dync1h1, similar to human mutations, show profoundly abnormal mitochondrial morphology associated with the loss of mitofusin 1. Furthermore, heterozygous Dync1h1 mutant mice display progressive mitochondrial dysfunct...
Exercise counteracts declining hippocampal function in aging and Alzheimer's disease.
Alzheimer's disease (AD) afflicts more than 5.4 million Americans and ranks as the most common type of dementia (Thies and Bleiler, 2011), yet effective pharmacological treatments have not been identified. Substantial evidence indicates that physical activity enhances learning and memory for people...
Mouse models of gene-environment interactions in schizophrenia.
Gene-environment interactions (GEIs) likely play significant roles in the pathogenesis of schizophrenia and underlie differences in pathological, behavioral, and clinical presentations of the disease. Findings from epidemiology and psychiatric genetics have assisted in the generation of animal model...
Increased susceptibility to acetylcholine in the entorhinal cortex of pilocarpine-treated rats involves alterations in KCNQ channels.
We tested the hypothesis whether the ictogenic effect of ACh involves alterations of KCNQ channels. In horizontal temporo-hippocampal slices from pilocarpine-treated chronically epileptic rats, field potential recordings of epileptiform activity were performed in response to the application of ACh,...
ABCA1 influences neuroinflammation and neuronal death.
We investigated the cell-type specific role of ABCA1 in neuroinflammation in vivo using mice specifically lacking brain ABCA1 (ABCA1(-B/-B)) as well as mice lacking neuronal (ABCA1(-N/-N)) and astrocytic (ABCA1(-Ast/-Ast)) ABCA1. ABCA1(-B/-B) mice exhibit cortical astrogliosis, increased inflammator...
Reduced paired pulse depression in the basal ganglia of dystonia patients.
We found that there was less paired pulse depression of local field evoked potentials in the basal ganglia output nuclei of dystonia patients compared with Parkinson's disease patients on dopaminergic medication. Paired pulse depression could be restored following focal high frequency stimulation (H...
Transcriptional dysregulation and impairment of PHOX2B auto-regulatory mechanism induced by polyalanine expansion mutations associated with ...
We tested the transcriptional activity of wild-type and mutant proteins on the PHOX2B gene promoter, and found that the transactivation ability of proteins with polyalanine expansions decreased as a function of the length of the expansion, whereas DNA binding was severely affected only in the case o...