Abstract:
:Amyotrophic lateral sclerosis (ALS) has become an increasingly attractive area for the pharmaceutical industry, the most experimentally tractable of the neurodegenerative diseases. Mechanisms underlying cell death in ALS are likely to be important in more common but more complex disorders. Riluzole, the only drug launched for treatment ALS is currently undergoing industrial trials for Alzheimer's, Parkinson's, Huntington disease, stroke and head injury. Other compounds in Phase III testing for ALS (mecamserin, xaliproden, gabapentin) are also in trials for other neurodegenerative disorders. Mechanisms of action of these advanced compounds are limited to glutamate antagonism, direct or indirect growth factor activity, as well as GABA agonism and interaction with calcium channels. A broader range of mechanisms is represented by compounds in Phase I trials: glutamate antagonism (dextramethorphan/p450 inhibitor; talampanel), growth factors (leukemia inhibiting factor; IL-1 receptor; encapsulated cells secreting CNTF) and antioxidants (TR500, a glutathione-repleting agent; recombinant superoxide dismutase; procysteine.) An even broader range of mechanisms is being explored in preclinical discovery programs. Recognition of the difficulties associated with delivery of protein therapeutics to the CNS has led to development of small molecules interacting either with neurotrophin receptors or with downstream intracellular signalling pathways. Other novel drug targets include caspaces, protein kinases and other molecules influencing apoptosis. High-throughput screens of large libraries of small molecules yield lead compounds that are subsequently optimized by chemists, screened for toxicity, and validated before a candidate is selected for clinical trials. The net is cast wide in early discovery efforts, only about 1% of which result in useful drugs at the end of a decade-long process. Successful discovery and development of novel drugs will increasingly depend on collaborative efforts between the academy and industry.
journal_name
J Neurol Scijournal_title
Journal of the neurological sciencesauthors
Hurko O,Walsh FSdoi
10.1016/s0022-510x(00)00419-6subject
Has Abstractpub_date
2000-11-01 00:00:00pages
21-8issue
1-2eissn
0022-510Xissn
1878-5883pii
S0022-510X(00)00419-6journal_volume
180pub_type
杂志文章,评审abstract::Drivers with cognitive impairment are at increased odds for vehicular crashes. Rear-end collisions (REC) are among the most common crash types. We tested REC avoidance in 61 drivers with mild Alzheimer's disease (AD) and 115 elderly controls using a high-fidelity interactive driving simulator. After a segment of uneve...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2006.08.011
更新日期:2006-12-21 00:00:00
abstract::We report the clinical features, electrophysiological findings and genetic characteristics of the first two Taiwanese siblings ever reported with sialidosis type I. We also provide a 10-year follow-up result. Enzymological analysis revealed a primary sialidase deficit. The back-averaged electroencephalography demonstr...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2006.03.013
更新日期:2006-08-15 00:00:00
abstract:UNLABELLED:The King-Devick (KD) oculomotor test has recently been advocated for sideline diagnosis of concussion. Although visual processing and performance are often impaired in concussion patients, the utility of KD as a concussion diagnostic tool is not validated. PURPOSE:To examine the diagnostic value of KD, by c...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2013.08.015
更新日期:2013-11-15 00:00:00
abstract::In our study, mitochondria were isolated from skeletal muscle in 2-, 3-, 4-, 6-, 8-, and 12-week-old normal (C57BL6j dy/+), and 4-, 8-, and 12-week-old dystrophic (C57BL6j dy/dy) mice and in normal subjects and patients with Duchenne or Becker muscular dystrophy. A deficit was observed in a calcium-specific mitochondr...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(89)90116-0
更新日期:1989-05-01 00:00:00
abstract::We conducted an extended clinical evaluation of localized proton magnetic resonance spectroscopy (MRS) of the brain, performed on various brain diseases using short stimulated echo times. Pathologies studied were mainly multiple sclerosis, stroke, leukoaraiosis, AIDS-related leukoencephalopathies and glial tumors. Oth...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(93)90101-4
更新日期:1993-09-01 00:00:00
abstract:OBJECTIVE:A recent nationwide survey of myelitis with atopic diathesis in Japan disclosed that the disease frequently shows a chronic persistent course. A neuropathological study of the spinal cord also revealed chronic active inflammation. Since the effects of various immunotherapies have not been studied extensively ...
journal_title:Journal of the neurological sciences
pub_type: 临床试验,杂志文章
doi:10.1016/j.jns.2004.08.001
更新日期:2004-12-15 00:00:00
abstract::Low 25-hydroxy vitamin D (25-[OH]-D) serum concentrations have been associated with higher disease activity in multiple sclerosis (MS) patients. In a large cross-sectional study we assessed the vitamin D status in MS patients in relation to seasonality and relapse rate. 415 MS-patients (355 relapsing-remitting MS and ...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2017.01.059
更新日期:2017-04-15 00:00:00
abstract::In the case reported, an overproduction of aldosterone was accompanied by paretic attacks, a decrease in the serum potassium level, and in muscle tone and the deep tendon reflexes. The decrease of serum potassium level was consistent, but moderate, being to just below the normal lower limit. Loading with carbohydrate ...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(77)90017-x
更新日期:1977-07-01 00:00:00
abstract::Glucose-regulated protein (GRP) 94 is a member of the stress protein family, which is localized in the endoplasmic reticulum (ER). Spinal cord injury (SCI) induced ER stress that results in apoptosis. However, the role of GRP94 in injury of the central nervous system remains unknown. In this study, we performed SCI in...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2011.06.024
更新日期:2011-10-15 00:00:00
abstract::The significance of P300 in investigation of the cognitive changes characteristic of aging and dementia is well established. But some controversies about sensitivity and specificity of P300 latency prolongation in detection of dementia still exist, and its predictive value and specificity in "real" clinical situations...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章,评审
doi:10.1016/0022-510x(95)00093-h
更新日期:1995-08-01 00:00:00
abstract::Intravascular lymphoma (IVL) is a rare disorder characterized by the aggregation of malignant large cell lymphoma cells in small vessels. Neurological manifestations are typically the initial and, often the only, clinically obvious consequences of this malignancy. Diagnosis is dependent on biopsy or postmortem demonst...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2005.01.001
更新日期:2005-05-15 00:00:00
abstract::We examined insulin-like growth factor I (IGF-I)-dependent phosphorylation and protein tyrosine kinase (PTK) activity in cerebellar cortex of normal humans, patients with olivopontocerebellar atrophy (OPCA) ("C" kindred) and in lurcher mutant mouse, a suggested animal model for OPCA. PTK activity and IGF-I-dependent p...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(94)90008-6
更新日期:1994-06-01 00:00:00
abstract:BACKGROUND:Previous studies to estimate burden of neurological disorders in Africa are limited to inpatients in urban hospitals. The spectrum of neurological conditions in rural Africa remains unclear. OBJECTIVE:To determine the spectrum of neurological presentations in an outpatient setting in rural Zimbabwe. METHOD...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2016.01.065
更新日期:2016-03-15 00:00:00
abstract::Familial hemiplegic migraine type 1, spinocerebellar ataxia type 6 (SCA6) and episodic ataxia type 2 (EA2) are allelic disorders associated with mutations in the CACNA1A gene, which encodes the alpha1 subunit of the P/Q-type calcium channel (Ca(V)2.1). SCA6 and EA2 share a number of clinical features, such as prominen...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2007.01.008
更新日期:2007-03-15 00:00:00
abstract::The mirror system includes a group of neurons in the monkey cortex that discharge both when a movement is executed and when that same movement is observed. An equivalent system in humans has been proposed to mediate action and emotion understanding, being therefore related to theory of mind. Theory of mind (TOM) is th...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.jns.2011.07.030
更新日期:2011-11-15 00:00:00
abstract:PURPOSE:To investigate the clinical characteristics and outcomes of myelin oligodendrocyte glycoprotein antibody-seropositive optic neuritis (MOG-ON) in patients with varying ages of onset in China. METHODS:Patients displaying symptoms of MOG-ON were recruited from the Neuro-ophthalmology Department in the Chinese Peo...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2019.03.014
更新日期:2019-05-15 00:00:00
abstract::Hallucinations and psychosis can be a part of Parkinson's disease and are considered to be a nonmotor symptom or a neuropsychiatric complication of the disease. Hallucinations of different modalities and delusions can occur beyond the common visual hallucinations. The various types of hallucinations and psychotic symp...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.jns.2017.01.014
更新日期:2017-03-15 00:00:00
abstract::We treated a female patient with West syndrome caused by thiamine-responsive pyruvate dehydrogenase complex (PDHC) deficiency. Infantile spasms occurred in association with elevated blood and CSF lactate concentrations; these symptoms disappeared when lactate concentrations had been lowered by treatment with concomita...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0022-510x(99)00250-6
更新日期:1999-12-01 00:00:00
abstract:BACKGROUND:Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disorder of the central nervous system. NMO and its abortive forms are referred to as NMO spectrum disorders (NMOSD). NMOSD are mostly associated with antibodies to aquaporin-4 (AQP4-IgG). However, recent studies have demonstrated antibodies to m...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2017.08.3254
更新日期:2017-10-15 00:00:00
abstract::Since Alzheimer's disease (AD) is becoming the prevalent dementia in the whole world, more underlying mechanisms are emerging. Long time has the transcription factor NF-κB been identified to participate in AD pathogenesis, various studies have focused on the causes and effects of AD that are linked to NF-κB. In this r...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.jns.2016.05.022
更新日期:2016-07-15 00:00:00
abstract::We describe a 54-year-old diabetic woman who developed ischemic optic neuropathy followed by acute retinal necrosis and multiple areas of focal venous beading. Vitreous fluid contained amplifiable VZV DNA but not HSV-1, CMV or toxoplasma DNA. The clinical presentation was remarkable for jaw claudication and intermitte...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2012.12.021
更新日期:2013-02-15 00:00:00
abstract::Fatigue is a common symptom in patients with neurologic disease. Mechanisms of fatigue are still incompletely understood. In this paper, we review recent studies of fatigue in common neurologic conditions and discuss therapeutic interventions. In particular, the role of therapeutic exercise is examined in both health ...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.jns.2005.11.012
更新日期:2006-03-15 00:00:00
abstract::Clinical data are presented of 63 artificially ventilated Guillain-Barré patients. About half of them had an antecedent event. In 57% the disease was heralded by sensory symptoms. The mean progressive phase lasted 12 days, the plateau 12 days and the recovery phase 568 days. In all patients one or more cranial nerves ...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(91)90303-o
更新日期:1991-08-01 00:00:00
abstract::A nitric oxide releasing compound, NOC-18, was injected intrathecally in order to determine the role of NO in spinal nociceptive mechanisms in rats. The nociceptive threshold was evaluated by the radiant heat tail-flick test. The effects of intrathecal injection of N-nitro-L-arginine methyl ester (L-NAME), an NO synth...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/s0022-510x(97)00188-3
更新日期:1997-12-09 00:00:00
abstract::Asia is the most populous region in the world and its rapidly growing societies are the sources of global development. However, accompanying this rapid growth is aging of the population with increasing occurrence of diseases, of which dementia is the most prominent, which provide major challenges to healthcare systems...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.jns.2012.07.023
更新日期:2012-10-15 00:00:00
abstract:OBJECTIVE:To describe the phenotype of individuals with intermediate allele (IA) CAG repeat length in the huntingtin (HTT) gene evaluated at the Parkinson's Disease Center and Movement Disorders Clinic (PDCMDC) at Baylor College of Medicine (BCM). BACKGROUND:Huntington disease (HD) is caused by a mutation in the HTT g...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2019.05.010
更新日期:2019-07-15 00:00:00
abstract::We have compared plasma redox status of coenzyme Q-10 in 20 sporadic amyotrophic lateral sclerosis (sALS) patients with those in 20 healthy age/sex-matched controls. A significant increase in the oxidized form of coenzyme Q-10 (sALS=109.3+/-95.2 nM; controls=23.3+/-7.5 nM, P=0.0002) and in the ratio of oxidized form o...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2004.09.030
更新日期:2005-01-15 00:00:00
abstract:BACKGROUND:As available disease-modifying therapies (DMTs) increase, evaluating benefit/risk presents greater difficulties, requiring people with MS (PwMS) to play crucial roles in choosing treatment. Although individual attitude toward risk may predict this evaluation, its relation to personality is little studied in ...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2020.117064
更新日期:2020-10-15 00:00:00
abstract:OBJECTIVE:To evaluate the role of balance training on Force Platform with Visual Feedback technique (FPVF) in improving balance and functional outcome in chronic stroke survivors. DESIGN:Prospective, repeated measure study. SETTINGS:Neurological rehabilitation department of a tertiary research center. PARTICIPANTS:F...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/j.jns.2009.08.051
更新日期:2009-12-15 00:00:00
abstract::The expression of class II antigen was studied in sural nerve biopsies from patients with peripheral neuropathies. These included patients with chronic demyelinating polyradiculoneuropathy (CIDP), non-immune mediated neuropathies of diverse etiologies and controls without evidence of neuropathy. The major finding in C...
journal_title:Journal of the neurological sciences
pub_type: 杂志文章
doi:10.1016/0022-510x(91)90065-f
更新日期:1991-04-01 00:00:00