Abstract:
:Charcot-Marie-Tooth (CMT) neuropathies are inherited neuromuscular disorders caused by a length-dependent neurodegeneration of peripheral nerves. More than 900 mutations in 60 different genes are causative of the neuropathy. Despite significant progress in therapeutic strategies, the disease remains incurable. The increasing number of genes linked to the disease, and their considerable clinical and genetic heterogeneity render the development of these strategies particularly challenging. In this context, cellular and animals models provide powerful tools. Efficient motor and sensory tests have been developed to assess the behavioral phenotype in transgenic animal models (rodent and fly). When these models reproduce a phenotype comparable to CMT, they allow therapeutic approaches and the discovery of modifiers and biomarkers. In this review, we describe the most convincing transgenic rodent and fly models of CMT and how they can lead to clinical trial. We also discuss the challenges that the research, the clinic, and the pharmaceutical industry will face in developing efficient and accessible treatment for CMT patients.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Bouhy D,Timmerman Vdoi
10.1002/ana.23987subject
Has Abstractpub_date
2013-09-01 00:00:00pages
391-6issue
3eissn
0364-5134issn
1531-8249journal_volume
74pub_type
杂志文章,评审abstract::Five patients with rapidly evolving, severe weakness had an unusual myopathy with virtually complete loss of myosin in 5 to 40% of muscle fibers. Three of the 5 patients began to develop weakness 1 to 2 weeks after lung transplantation. The fourth became weak after a febrile illness. The fifth presented with diabetic ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410350306
更新日期:1994-03-01 00:00:00
abstract::In 9 patients with progressive supranuclear palsy and in 27 controls, dopamine and homovanillic acid concentrations, choline acetyltransferase (CAT) activity, and the number of [3H]spiperone and [3H]quinuclidinyl benzilate binding sites were measured post mortem in the striatum (caudate nucleus, putamen, and nucleus a...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410180503
更新日期:1985-11-01 00:00:00
abstract::Adult polyglucosan body disease (APBD) is a late-onset, slowly progressive disorder of the nervous system caused by glycogen branching enzyme (GBE) deficiency in a subgroup of patients of Ashkenazi Jewish origin. Similar biochemical finding is shared by glycogen storage disease type IV (GSD IV) that, in contrast to AP...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410440604
更新日期:1998-12-01 00:00:00
abstract::A 50,000-dalton polypeptide has been purified from fractions enriched with neurofibrillary tangles of paired helical filaments from human autopsy specimens of Alzheimer disease and senile dementia of the Alzheimer type. An antiserum to this polypeptide was raised in a rabbit. This antiserum formed an immunoprecipitati...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410060612
更新日期:1979-12-01 00:00:00
abstract::Most neurodegenerative disorders are thought to result primarily from the accumulation of misfolded proteins, which interfere with protein homeostasis in neurons. For a subset of diseases, however, noncoding regions of RNAs assume a primary toxic gain-of-function, leading to degeneration in many tissues, including the...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.21948
更新日期:2010-03-01 00:00:00
abstract::The functional status of the globus pallidus internal segment (GPi) plays a key role in mediating the effects of antiparkinsonian drugs. During long-term levodopa therapy, patients develop abnormal movements, dyskinesias, the pathophysiological basis of which is poorly understood. We recorded single cells in the GPi o...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199911)46:5<732::aid-ana8>3.0.co
更新日期:1999-11-01 00:00:00
abstract:OBJECTIVE:Central nervous system pathology in multiple sclerosis includes both focal inflammatory perivascular injury and injury to superficial structures, including the subpial region of the cortex, which reportedly exhibits a gradient of damage from the surface inward. We assessed how early in the multiple sclerosis ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25429
更新日期:2019-03-01 00:00:00
abstract:OBJECTIVE:To evaluate the ability of mesenchymal stem cells (MSCs), a subset of adult stem cells from bone marrow, to cure experimental autoimmune encephalomyelitis. METHODS:The outcome of the injection of MSCs, in mice immunized with the peptide 139-151 of the proteolipid protein (PLP), was studied analyzing clinical...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21076
更新日期:2007-03-01 00:00:00
abstract::Persons affected with tuberous sclerosis complex (TSC) develop a wide range of neurological abnormalities including aberrant neuronal migration and seizures. In an effort to model TSC-associated central nervous system abnormalities in mice, we generated two independent lines of astrocyte-specific Tsc1 conditional knoc...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10283
更新日期:2002-09-01 00:00:00
abstract::We hypothesized that automated assessment of collaterals on computed tomography perfusion can predict the rate of infarct growth during transfer from a primary to a comprehensive stroke center for endovascular stroke treatment. We identified consecutive patients (N = 28) and assessed their collaterals based on the hyp...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25320
更新日期:2018-10-01 00:00:00
abstract::We present a patient with hemidystonia and an abnormality of the contralateral basal ganglion seen only with positron emission tomography. A 50-year-old sinistral man suffered minor trauma to the right side of his head and neck. Within 20 minutes he developed paroxysmal intermittent dystonic posturing of his right fac...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410150303
更新日期:1984-03-01 00:00:00
abstract::A prospective study of 162 patients with adult-onset chronic epilepsy revealed 4 in whom computed tomographic scanning was the only diagnostic test that detected the presence of a surgically correctable cerebral lesion. These patients had suffered from seizures for 1 to 14 years and at the time of operation demonstrat...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410070411
更新日期:1980-04-01 00:00:00
abstract::A 37-year-old woman with primary Sjögren syndrome developed mixed cryoglobulinemia and systemic vasculitis. Subarachnoid hemorrhage occurred as a result of necrotizing anterior spinal arteritis. Although rarely seen in mixed cryoglobulinemia, central nervous system complications have recently been documented in Sjögre...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410110614
更新日期:1982-06-01 00:00:00
abstract::This study assessed whether or not levodopa induces dyskinesias in normal (ie, unlesioned) squirrel monkeys. All six animals treated twice daily with levodopa (15 mg/kg with carbidopa by oral gavage) for two weeks developed choreoathetoid dyskinesias, whereas none of the vehicle-treated animals displayed any abnormal ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.1099
更新日期:2001-08-01 00:00:00
abstract::The fate of neurofilament (NF) proteins was examined in sections of nerves from rats that survived for 3 to 90 days following nerve transection, using anti-NF monoclonal antibodies and immunohistochemical techniques. The same methods were also applied to twenty-three human nerve biopsy specimens. Granular debris with ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410160312
更新日期:1984-09-01 00:00:00
abstract::Microelectrode recording methods for stereotactic localization of the subthalamic nucleus (STN) and surrounding structures are described. These methods accurately define targets for chronic deep brain stimulation in the treatment of Parkinson's disease. Mean firing rates and a burst index were determined for all recor...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410440407
更新日期:1998-10-01 00:00:00
abstract::Patients with the acquired immunodeficiency syndrome (AIDS) commonly display evidence of gross cerebral atrophy, but its true incidence and pathophysiology in the general AIDS population are unknown. In this study, we measured cerebrospinal fluid (CSF) spaces in 64 consecutively autopsied patients with AIDS, compared ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410320107
更新日期:1992-07-01 00:00:00
abstract::We here report the second and third mutations in alphaB-crystallin causing myofibrillar myopathy. Two patients had adult-onset muscle weakness. Patient 1 had cervical, limb girdle, and respiratory muscle weakness and died of respiratory failure. Patient 2 had proximal and distal leg muscle weakness. Both had myopathic...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10767
更新日期:2003-12-01 00:00:00
abstract::The Pilot Stroke Data Bank obtained information on 94 patients with intracerebral hemorrhage. These data were used to identify factors predictive of 30-day outcome from among 85 demographic, historical, clinical, and laboratory variables generally available to clinicians on the day of admission. The 9 univariate facto...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410240213
更新日期:1988-08-01 00:00:00
abstract::Spinal muscular atrophy (SMA) is a motor neuron disease caused by dysfunction of the survival motor neuron (SMN) gene. Human SMN gene is present in duplicated copies: SMN1 and SMN2. More than 95% of patients with SMA lack a functional SMN1 but retain at least one copy of SMN2. Unlike SMN1, SMN2 is primarily transcribe...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20548
更新日期:2005-08-01 00:00:00
abstract::We describe a kindred with 7 confirmed and 2 probable cases of subacute dementia accompanied by myoclonus. The inheritance pattern is consistent with autosomal dominance and shows anticipation. The pathological changes involve marked gliosis with neuronal loss of the dorsomedial and midline thalamic nuclei, with lesse...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200209
更新日期:1986-08-01 00:00:00
abstract::Protease-resistant prion protein, total prion protein, and glial fibrillary acidic protein were measured in various brain regions from 9 subjects with fatal familial insomnia. Six were homozygotes methionine/methionine at codon 129 (mean duration, 10.7 +/- 4 months) and 3 were heterozygotes methionine/valine (mean dur...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410380107
更新日期:1995-07-01 00:00:00
abstract::Friedreich's ataxia (FA) is the most frequently inherited ataxia. To test the hypothesis that iron is increased in the cerebellum of patients with FA, we developed a multigradient echo magnetic resonance sequence for the three-dimensional imaging of brain iron-induced contrast. Relaxation rate (R2*) values in the unaf...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199907)46:1<123::aid-ana19>3.0.c
更新日期:1999-07-01 00:00:00
abstract::Homocarnosine, a dipeptide of gamma-aminobutyric acid (GABA) and histidine, is thought to be an inhibitory neuromodulator synthesized in subclasses of GABAergic neurons. Homocarnosine is present in human brain in greater amounts (0.4-1.0 micromol/g) than in other animals. The antiepileptic drug vigabatrin increases hu...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章
doi:10.1002/ana.410440614
更新日期:1998-12-01 00:00:00
abstract:OBJECTIVE:To determine whether cerebrovascular risk factors are associated with subsequent diagnoses of Parkinson disease, and whether these associations are similar in magnitude to those with subsequent diagnoses of Alzheimer disease. METHODS:This was a retrospective cohort study using claims data from a 5% random sa...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25564
更新日期:2019-10-01 00:00:00
abstract::Stereotaxic injection of kainic acid into rat striatum produces neuronal degeneration and neurochemical alterations resembling Huntington's disease (HD). Since correction of the deficiency in gamma-aminobutyric acid (GABA) in HD may be of therapeutic value, the efficacy of drugs that inhibit the GABA-degrading enzyme ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410020407
更新日期:1977-10-01 00:00:00
abstract::The prevalence of migraine is much greater in female than male individuals. Cortical spreading depression (CSD) is thought to be a fundamental mechanism of migraine, and CSD in rodents is used as a model for migraine. We used optical intrinsic signal imaging and electrophysiological techniques to investigate CSD in C5...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21138
更新日期:2007-06-01 00:00:00
abstract:OBJECTIVE:Gray matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in multiple sclerosis (MS), but can these changes be identified in the patient early in the disease course? METHODS:To identify possible biomarkers linking meningeal inflammat...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25197
更新日期:2018-04-01 00:00:00
abstract::The incidence of periventricular-intraventricular hemorrhage (PV-IVH) in a group of 460 preterm infants with birth weight less than 2,250 gm, studied by cranial ultrasonography, was 39%. Sixty-four (36%) of the infants with periventricular-intraventricular hemorrhage had, in addition, periventricular intraparenchymal ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410150315
更新日期:1984-03-01 00:00:00
abstract::Patterns of brain dysgenesis that resemble those in the Zellweger syndrome were demonstrated in a boy with an isolated defect of the peroxisomal bifunctional enzyme. There was bilateral centrosylvian pachygyria and polymicrogyria, diffuse hemispheric hypomyelination with heterotopic neurons, Purkinje cell heterotopias...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410390218
更新日期:1996-02-01 00:00:00