23,525 research outputs found
Large-scale gene-expression studies and the challenge of multiple sclerosis.
In multiple sclerosis, a complex neurodegenerative disorder, a combination of genetic and environmental factors results in inflammation and myelin damage. Recent transcription-profiling studies have found distinct gene-expression patterns in diseased tissue; such large-scale studies at different stages of the disease are contributing to understanding multiple sclerosis and developing effective therapy
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Equine degenerative myeloencephalopathy: prevalence, impact, and management.
Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy is an inherited neurodegenerative disorder affecting many horse breeds. Clinical signs include a symmetric ataxia and an abnormal stance at rest, similar to cervical vertebral compressive myelopathy, equine protozoal myeloencephalitis, and equine herpesvirus 1 myeloencephalopathy. This review will provide an update on the disease prevalence, management, impact, and ongoing research
Epigenetic-based treatment as a potential strategy to treat Friedreich’s ataxia
Friedreich’s ataxia (FRDA) is an autosomal recessive neurodegenerative disorder. It is
the most common inherited ataxia in Europe. The neurodegeneration is progressive and
normally, within 15-20 years, the patient becomes wheel-chair bound, and ultimately, is totally
incapacitated. Affected individuals normally succumb from heart complications. Frataxin (FXN)
is a mitochondrial protein that is deficient in FRDA. The deficiency is caused by a mutation
within the first intron of the FXN gene which codes for frataxin. Epigenetic mechanisms are
responsible in FRDA and epigenetic-based treatment is a potential new strategy to treat FRDA.peer-reviewe
Generation of induced pluripotent stem cell line, CSSi004-A (2962), from a patient diagnosed with Huntington's disease at the presymptomatic stage
Huntington's disease (HD) is an incurable, autosomal dominant, hereditary neurodegenerative disorder that typically manifests itself in midlife. This pathology is linked to the deregulation of multiple, as yet unknown, cellular processes starting before HD onset. A human iPS cell line was generated from skin fibroblasts of a subject at the presymptomatic life stage, carrying a polyglutamine expansion in HTT gene codifying Huntingtin protein. The iPSC line contained the expected CAG expansion, expressed the expected pluripotency markers, displayed in vivo differentiation potential to the three germ layers and had a normal karyotype
Neurodegenerative Disorder Risk in Krabbe Disease Carriers
Krabbe disease (KD) is a rare autosomal recessive disorder caused by mutations in the galactocerebrosidase gene (GALC). Defective GALC causes aberrant metabolism of galactolipids present almost exclusively in myelin, with consequent demyelinization and neurodegeneration of the central and peripheral nervous system (NS). KD shares some similar features with other neuropathies and heterozygous carriers of GALC mutations are emerging with an increased risk in developing NS disorders. In this work, we set out to identify possible variations in the proteomic profile of KD-carrier brain to identify altered pathways that may imbalance its homeostasis and that may be associated with neurological disorders. The differential analysis performed on whole brains from 33-day-old twitcher (galc (-/-)), heterozygous (galc (+/-)), and wild-type mice highlighted the dysregulation of several multifunctional factors in both heterozygous and twitcher mice. Notably, the KD-carrier mouse, despite its normal phenotype, presents the deregulation of vimentin, receptor of activated protein C kinase 1 (RACK1), myelin basic protein (MBP), 2 ',3 '-cyclic-nucleotide 3 '-phosphodiesterase (CNP), transitional endoplasmic reticulum ATPase (VCP), and N-myc downstream regulated gene 1 protein (NDRG1) as well as changes in the ubiquitinated-protein pattern. Our findings suggest the carrier may be affected by dysfunctions classically associated with neurodegeneration: (i) alteration of (mechano) signaling and intracellular trafficking, (ii) a generalized affection of proteostasis and lipid metabolism, with possible defects in myelin composition and turnover, and (iii) mitochondrion and energy supply dysfunctions
Developmental aspects of FXAND in a man with the FMR1 premutation.
BackgroundFragile X mental retardation 1 (FMR1) premutation can cause developmental problems including autism spectrum disorder (ASD), social anxiety, depression, and attention deficit hyperactivity disorder (ADHD). These problems fall under an umbrella term of Fragile X-associated Neuropsychiatric Disorders (FXAND) and is separate from Fragile X-associated Tremor/Ataxia syndrome (FXTAS), a neurodegenerative disorder.Methods/clinical caseA 26-year-old Caucasian male with the Fragile X premutation who presented with multiple behavior and emotional problems including depression and anxiety at 10Â years of age. He was evaluated at 13, 18, and 26Â years old with age-appropriate cognitive assessments, psychiatric evaluations, and an MRI of the brain.ResultsThe Autism Diagnostic Observation Scale (ADOS) was done at 13Â years old and showed the patient has autism spectrum disorder (ASD). An evaluation at 18Â years old showed a full-scale IQ of 64. A Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) performed at 26Â years old confirmed the previous impression of social anxiety disorder, agoraphobia disorder, and selective mutism. His MRI acquired at 26Â years old showed enlarged ventricles, increased frontal subarachnoid spaces, and hypergyrification.ConclusionThis is an exemplary case of an FMR1 premutation carrier with significant psychiatric and cognitive issues that demonstrates Fragile X-associated Neuropsychiatric Disorders (FXAND) as separate from the other well-known premutation disorders
Kufor-Rakeb syndrome, pallido-pyramidal degeneration with supranuclear upgaze paresis and dementia, maps to 1p36
Kufor-Rakeb syndrome is an autosomal
recessive nigro-striatal-pallidal-pyramidal
neurodegeneration. The onset is in the
teenage years with clinical features of Parkinson’s
disease plus spasticity, supranuclear
upgaze paresis, and dementia. Brain
scans show atrophy of the globus pallidus
and pyramids and, later, widespread cerebral
atrophy. We report linkage in Kufor-
Rakeb syndrome to a 9 cM region of
chromosome 1p36 delineated by the markers
D1S436 and D1S2843, with a maximum
multipoint lod score of 3.6.
(J Med Genet 2001;38:680–682
Targeted molecular therapeutics for Parkinson's Disease: A role for antisense oligonucleotides?
Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by marked heterogeneity in clinical symptoms and a complex genetic background..
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